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Background The ultrasensitive monitoring strategy of zearalenone (ZEN) is essential and desirable for food safety and human health. In the present study, a coupling of gold nanoparticles-DNA barcode and direct competitive immunoassay-based real-time polymerase chain reaction signal amplification (RT-IPCR) for ZEN close to the sensitivity of PCR-like levels is described and evaluated. Results The RT-IPCR benefited from the use of a DNA barcode and RT-PCR detection strategy, thus resulting in ultrasensitive and simple detection for ZEN. Under the optimal RT-IPCR, the linear range of detection was from 0.5 to 1000 pg mL-1 and the limit of detection was 0.5 pg mL-1 , which was 400-fold lower than the enzyme-linked immunosorbent assay. The detection procedure was simplified and the detection time was shortened. The specificity, accuracy and precision of the RT-IPCR confirmed a high performance. ZEN-positive contamination levels were from 0.056 to 152.12 ng g-1 by the RT-IPCR, which was demonstrated to be highly reliable by liquid chromatography-tandem mass spectrometry. Conclusion The proposed RT-IPCR could be used as an alternative for detecting ZEN with satisfactory ultrasensitivity, simplicity, low cost and high-throughput. The present study could provide a strategy for the ultrasensitive detection of the small molecule with a simple and practical approach, which has significant appeal and application prospects.

The Dongping gold deposit is located near the center of the northern margin of the North China Craton. It is hosted in the Shuiquangou syenite and characterized by large amounts of tellurides. Numerous studies have addressed this deposit; the mineral paragenesis and ore-forming processes, however, are still poorly studied. In this contribution, a new mineral paragenesis has been evaluated to further understand ore formation, including sulfides (pyrite, chalcopyrite, galena, sphalerite, molybdenite, and bornite), tellurides (altaite, calaverite, hessite, muthmannite, petzite, rucklidgeite, sylvanite, tellurobismuthite, tetradymite, and volynskite), and native elements (tellurium and gold). Molybdenite, muthmannite, rucklidgeite, and volynskite are reported for the first time in this deposit. We consider the Dongping gold deposit mainly formed in the Devonian, and the ore-forming processes and the physicochemical conditions for ore formation can be reconstructed based on our newly identified ore paragenesis, that is, iron oxides -> (CO₂ effervescence) -> sulfides -> (fTe₂/fS₂ ratio increase) -> Pb-Bi-tellurides -> (condensation of H₂Te vapor) -> Au-Ag-tellurides -> (mixing with oxidizing water) -> carbonate and microporous gold -> secondary minerals -> secondary minerals. The logfO₂ values increase from the early to late stages, while the fH₂S and logfS₂ values increase initially and then decrease. CO₂ effervescence is the main mechanism of sulfides precipitation; this sulfidation and condensation of H₂Te vapor lead to deposition of tellurides. The development of microporous gold indicates that the deposit might experience overprint after mineralization. The Dongping gold deposit has a close genetic relationship with the Shuiquangou syenite, and tellurium likely originated from Shuiquangou alkaline magmatic degassing.

Human cytomegalovirus (CMV) is a ubiquitous, persistent beta herpesvirus. CMV infection contributes to the accumulation of functional antigen‐specific CD8(+) T‐cell pools with an effector‐memory phenotype and enrichment of these immune cells in peripheral organs. We review here this ‘memory T‐cell inflation’ phenomenon and associated factors including age and sex. ‘Collateral damage’ due to CMV‐directed immune reactivity may occur in later stages of life – arising from CMV‐specific immune responses that were beneficial in earlier life. CMV may be considered an age‐dependent immunomodulator and a double‐edged sword in editing anti‐tumour immune responses. Emerging evidence suggests that CMV is highly prevalent in patients with a variety of cancers, particularly glioblastoma. A better understanding of CMV‐associated immune responses and its implications for immune senescence, especially in patients with cancer, may aid in the design of more clinically relevant and tailored, personalized treatment regimens. ‘Memory T‐cell inflation’ could be applied in vaccine development strategies to enrich for immune reactivity where long‐term immunological memory is needed, e.g. in long‐term immune memory formation directed against transformed cells.

Pulmonary artery-derived ventricular arrhythmia is gradually being recognized, which in a clinical context is recognized as an arterial ectopic beat. Our study aimed to provide new insights on the epidemiological characteristics, origin site, electrocardiogram (ECG) characteristics, intracardiac electrophysiological characteristics and radiofrequency catheter ablation (RFCA) strategies for pulmonary artery-derived ventricular arrhythmia. Patients with a distance between the origin site and the pulmonary valve of >10 mm have what is known as pulmonary trunk-derived ventricular arrhythmia, while patients with a distance between the origin site and the pulmonary valve of ≤10 mm have what is known as pulmonary sinus cusp-derived ventricular arrhythmia. It is very difficult to differentiate pulmonary artery-derived ventricular arrhythmia from right ventricular outflow tract-derived ventricular arrhythmia on ECGs as both share similar anatomical features, but pulmonary artery-derived ventricular arrhythmia shows obvious intracardiac electrophysiological characteristics. Currently, conclusions based on the epidemiological characteristics of pulmonary artery-derived ventricular arrhythmia, relationship between the origin site and the pulmonary valve, electrophysiological characteristics, and RFCA strategies are controversial and still need further study.

The Cuihongshan deposit is a giant Fe-polymetallic skarn deposit located in the northern zone of the Lesser Xing'an-Zhangguangcai Range (LXZR), NE China. It is predominantly hosted in skarn contact zones between marble and alkali-feldspar granites and monzogranites, with minor in fracture zones of granodiorites. Because of dense vegetation cover, complex intrusions, and contact relation between orebodies and rocks, the metallogenesis of the deposit is poorly understood. Here, we present detailed whole-rock geochemistry, zircon U-Pb geochronology of granitoids, and molybdenite Re-Os isotopic dating data. All of the granitoids in the Cuihongshan deposit area are silica and potassium rich, highly fractionated, showing affinities to high-fractionated I-type granites. However, compared with the other granitoids, the Late Triassic alkali-feldspar granites have higher differentiation index, stronger enrichment in F, W, Mo, Pb, Th, U, and volatiles with partial mineralization. The zircon U-Pb dating of the granodiorite, monzogranite, and alkali-feldspar granite yielded weighted average ages of 493 +/- 4, 194 +/- 1, and 204 +/- 1Ma, respectively. The Re-Os dating of molybdenites from the Cuibei and Cuizhong ore sections yielded isochron ages of 205 +/- 2 and 204 +/- 4Ma, respectively, which are consistent with the emplacement age of the alkali-feldspar granite. Combined with the lines of evidence from the contact relationship between the orebodies and alkali-feldspar granite, the disseminated mineralization and the enrichment in ore-forming elements and volatiles in the alkali-feldspar granite, these indicate that the Late Triassic alkali-feldspar granite rather than the monzogranite as previously reported, has a close genetic relationship with the Cuihongshan deposit. In addition, the alkali-feldspar granites occur as apophyses and dikes, but the Late Cambrian and Early Jurassic granitoids occur as batholiths. This indicates that, according to the theory that small intrusions form large deposits, a potential Late Triassic (similar to 204Ma) buried batholith might have provided abundant ore-forming materials. However, the top parts of the Late Cambrian and Early Jurassic granitoids have been denudated, which is unfavourable for significant deposit preservation and mineralization related to the 2 stages of granitoids. This study gives a significant suggestion that exposed, and blind apophyses and dikes should be further considered in the exploration and study of metal deposits in NE China. Three phases of mineralization occurred in the LXZR in the Triassic-Jurassic, namely, porphyry-skarn Cu-Mo polymetallic mineralization (similar to 250-240Ma), skarn Fe-Pb-Zn polymetallic mineralization (similar to 204-190Ma), and porphyry Mo polymetallic mineralization (similar to 180-160Ma). On the basis of regional data, the LXZR experienced subduction and collisional settings during similar to 260-185Ma and similar to 180-160Ma, respectively. Hence, the Early Triassic (similar to 250-240Ma) and Late Triassic-Early Jurassic (similar to 204-190Ma) mineralizations represented by the Baoshan and Cuihongshan deposits, respectively, are related to the early and late subduction of the oceanic plate between the Songliao and Jiamusi massifs beneath the Songliao Massif, respectively. This also indicates a potential mineralization in the LXZR in the Middle Triassic. However, the genesis of the late large-scale porphyry Mo polymetallic deposits (similar to 185-160Ma; e.g. , Daheishan, Luming, Huojihe, Xinghualong, Xingshan, and Wulugetushan deposits) is constrained by the collision of the Songliao and Jiamusi massifs.

Background Information Microtubule affinity-regulating kinase 4 (MARK4) deficiency has been reported to negatively regulate diet-induced obesity and to mitigate insulin resistance in knockout mice, and thus may play a role in metabolic syndrome. However, the details of the molecular mechanism have yet to be revealed and the impacts of MARK4 on apoptosis remain unexplored. This study investigated the role of Mark4 in the regulation of lipid accumulation and apoptosis in adipocytes and analysed signalling pathways involved. Results We found that Mark4 significantly up-regulated the expression of gene sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), acetyl-CoA carboxylase-α (ACCα) and peroxisome proliferator activated receptor-γ (PPARγ); and reduced the protein contents of adipose triglyceride lipase (ATGL), as evidenced by the dramatic increasing lipid droplet accumulation in 3T3-L1 cells. Furthermore, a terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) apoptosis assay showed that Mark4 triggered apoptosis of adipocytes; and apoptosis was confirmed by the decreased protein contents of B-cell lymphoma-2 (Bcl-2), full-length caspase-3 and full-length caspase-9, as well as the increased expression of Bax, cleaved caspase-3 and cleaved caspase-9. Analysis of special inhibitors allowed us to offer the following explanation for these impacts of Mark4: activation of Jun N-terminal kinase1 (JNK1) promoted both apoptosis and adipogenesis, whereas inhibition of the p38 mitogen-activated protein kinase (p38MAPK) pathway contributed to lipid accumulation alone. Conclusions Mark4 promotes adipogenesis in 3T3-L1 adipocytes by activating the JNK1 and inhibiting the p38MAPK pathway, and triggers apoptosis by activating the JNK1 pathway. We conclude that anti-Mark4 therapy targetted to inhibit lipid accumulation and apoptosis of adipocytes shows potential as a novel therapeutic strategy for treatment of obesity-associated metabolic complications.

We conducted a population-based case-control study in Connecticut women to test the hypothesis that genetic variations in DNA repair pathway genes may modify the relationship between body mass index (BMI) and risk of non-Hodgkin lymphoma (NHL). Compared to those with BMI

Obesity is associated with macrophage infiltration and metabolic inflammation, both of which promote metabolic disease progression. Melatonin is reported to possess anti-inflammatory properties by inhibiting inflammatory response of adipocytes and macrophages activation. However, the effects of melatonin on the communication between adipocytes and macrophages during adipose inflammation remain elusive. Here, we demonstrated melatonin alleviated inflammation and elevated α-ketoglutarate (αKG) level in adipose tissue of obese mice. Mitochondrial isocitrate dehydrogenase 2 (Idh2) mRNA level was also elevated by melatonin in adipocytes leading to increase αKG level. Further analysis revealed αKG was the target for melatonin inhibition of adipose inflammation. Moreover, sirtuin 1 (Sirt1) physically interacted with IDH2 and formed a complex to increase the circadian amplitude of Idh2 and αKG content in melatonin-inhibited adipose inflammation. Notably, melatonin promoted exosomes secretion from adipocyte and increased adipose-derived exosomal αKG level. Our results also confirmed that melatonin alleviated adipocyte inflammation and increased ratio of M2 to M1 macrophages by transporting of exosomal αKG to macrophages and promoting TET-mediated DNA demethylation. Furthermore, exosomal αKG attenuated signal transducers and activators of transduction-3 (STAT3)/NF-κB signal by its receptor oxoglutarate receptor 1 (OXGR1) in adipocytes. Melatonin also attenuated adipose inflammation and deceased macrophage number in chronic jet-lag mice. In summary, our results demonstrate melatonin alleviates metabolic inflammation by increasing cellular and exosomal αKG level in adipose tissue. Our data reveal a novel function of melatonin on adipocytes and macrophages communication, suggesting a new potential therapy for melatonin to prevent and treat obesity caused systemic inflammatory disease.

Pyroptosis is a proinflammatory form of cell death that is associated with pathogenesis of many chronic inflammatory diseases. Melatonin is substantially reported to possess anti-inflammatory properties by inhibiting inflammasome activation. However, the effects of melatonin on inflammasome-induced pyroptosis in adipocytes remain elusive. Here, we demonstrated that melatonin alleviated lipopolysaccharides (LPS)-induced inflammation and NLRP3 inflammasome formation in mice adipose tissue. The NLRP3 inflammasome-mediated pyroptosis was also inhibited by melatonin in adipocytes. Further analysis revealed that gasdermin D (GSDMD), the key executioner of pyroptosis, was the target for melatonin inhibition of adipocyte pyroptosis. Importantly, we determined that nuclear factor κB (NF-κB) signal was required for the GSDMD-mediated pyroptosis in adipocytes. We also confirmed that melatonin alleviated adipocyte pyroptosis by transcriptional suppression of GSDMD. Moreover, GSDMD physically interacted with interferon regulatory factor 7 (IRF7) and subsequently formed a complex to promote adipocyte pyroptosis. Melatonin also attenuated NLRP3 inflammasome activation and pyroptosis, which was induced by LPS or obesity. In summary, our results demonstrate that melatonin alleviates inflammasome-induced pyroptosis by blocking NF-κB/GSDMD signal in mice adipose tissue. Our data reveal a novel function of melatonin on adipocyte pyroptosis, suggesting a new potential therapy for melatonin to prevent and treat obesity caused systemic inflammatory response.

Melatonin is synthesized in the pineal gland and controls circadian rhythm of peripheral adipose tissue, resulting in changes in body weight. Although core regulatory components of clock rhythmicity have been defined, insight into the mechanisms of circadian rhythm-mediated proliferation in adipose tissue is still limited. Here, we showed that melatonin (20 mg/kg/d) promoted circadian and proliferation processes in white adipose tissue. The circadian amplitudes of brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (Bmal1, P