L-carnitine (LC) is well known for its antioxidant activity. In this study, we explored the potential mechanistic effects of LC supplementation on aged bovine oocytes in vitro. We showed that ...in-vitro maturation could enhance the subsequent developmental capacity of aging oocytes, when supplemented with LC. After in vitro fertilization, the blastocyst formation rate in the aged oocytes post-LC treatment significantly increased compared to that in untreated aged oocytes (29.23 ± 2.20% vs. 20.90 ± 3.05%). Furthermore, after LC treatment, the level of intracellular reactive oxygen species in aged oocytes significantly decreased, and glutathione levels significantly increased, compared to those in untreated aged oocytes. Mitochondrial membrane potential, the percentage of early apoptotic oocytes, and caspase-3 activity were significantly reduced in LC-treated aged oocytes compared to those in untreated aged oocytes. Furthermore, during in vitro aging, the mRNA levels of the anti-apoptotic genes, Bcl-xl and survivin in LC-treated aged oocytes were significantly higher than those in untreated aged oocytes. Overall, these results indicate that at least in in vitro conditions, LC can prevent the aging of bovine oocytes and improve the developmental capacity of bovine embryo.
The properties of fast radio bursts (FRBs) indicate that the physical origin of this type of astrophysical phenomenon is related to neutron stars. The first detected repeating source, FRB 121102, is ...associated with a persistent radio counterpart. In this paper, we propose that this radio counterpart could arise from a pulsar wind nebula powered by a magnetar without surrounding supernova ejecta. Its medium is a stratified structure produced by a progenitor wind. The model parameters are constrained by the spectrum of the counterpart emission, the size of the nebula, and the large but decreasing rotation measure (RM) of the repeating bursts. In addition, the observed dispersion measure is consistent with the assumption that all of the RM comes from the shocked medium.
Immunotherapies that target programmed cell death protein 1 (PD-1) and its ligand PD-L1 as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA4) have shown impressive clinical outcomes for ...multiple tumours. However, only a subset of patients achieves durable responses, suggesting that the mechanisms of the immune checkpoint pathways are not completely understood. Here, we report that PD-L1 translocates from the plasma membrane into the nucleus through interactions with components of the endocytosis and nucleocytoplasmic transport pathways, regulated by p300-mediated acetylation and HDAC2-dependent deacetylation of PD-L1. Moreover, PD-L1 deficiency leads to compromised expression of multiple immune-response-related genes. Genetically or pharmacologically modulating PD-L1 acetylation blocks its nuclear translocation, reprograms the expression of immune-response-related genes and, as a consequence, enhances the anti-tumour response to PD-1 blockade. Thus, our results reveal an acetylation-dependent regulation of PD-L1 nuclear localization that governs immune-response gene expression, and thereby advocate targeting PD-L1 translocation to enhance the efficacy of PD-1/PD-L1 blockade.
Background and Aims
Exposure to metals may promote the risk for cancers. We evaluated the associations of a broad spectrum of metals with gallbladder cancer (GBC) and gallstones.
Approach and Results
...A total of 259 patients with GBC, 701 patients with gallstones, and 851 population‐based controls were enrolled in Shanghai, China. A metallome panel was used to simultaneously detect 18 metals in serum through inductively coupled plasma–mass spectrometry. Logistic regression models were used to estimate crude or adjusted odds ratios (ORadj) with 95% confidence intervals (CIs) for the association between metal levels and gallbladder disease. Among the 18 metals tested, 12 were significantly associated with GBC and six with gallstones (Pcorrected < 0.002). Boron, lithium, molybdenum, and arsenic levels were associated with GBC compared to gallstones as well as with gallstones compared to population‐based controls. Elevated levels of cadmium, chromium, copper, molybdenum, and vanadium were positively associated with GBC versus gallstones; and the ORadj for the highest tertile (T3) compared to the lowest tertile (T1) ranged from 1.80 to 7.28, with evidence of dose–response trends (P < 0.05). Arsenic, boron, iron, lithium, magnesium, selenium, and sulfur were inversely associated with GBC, with the T3 versus T1 ORadj ranging from 0.20 to 0.69. Arsenic, boron, calcium, lithium, molybdenum, and phosphorus were negatively associated with gallstones, with the T3 versus T1 ORadj ranging from 0.50 to 0.75 (P < 0.05).
Conclusions
Metals were associated with both GBC and gallstones, providing cross‐sectional evidence of association across the natural history of disease. Longitudinal studies are needed to evaluate the temporality of metal exposure and gallbladder diseases and to investigate the mechanisms of disease pathogenesis.
Co3O4 with a high theoretical capacitance has been widely recognized as a promising electrode material for supercapacitor, but its poor electrical conductivity and stability limit its practical ...applications. Here, we developed an effective synthetic route to synthesize one-dimensional (1D) porous ZnO/Co3O4 heterojunction composites. Benefiting from the heterostructure to promote the charge transfer and protect Co3O4 from corrosion and the 1D porous structure to improve ion diffusion and prevent structural collapse in charge and discharge process, the as-prepared ZnO/Co3O4 composites exhibited an excellent capacitive performance and good cycling stability. The specific capacitance of the ZnO/Co3O4-450 (1135 F g–1 at 1 A g–1) was 1.4 times higher than that of Co3O4 (814 F g–1), and the high-rate performance for ZnO/Co3O4-450 was 4.9 times better than that of Co3O4. Also, approximately 83% of its specific capacitance was retained after 5000 cycles at 10 A g–1. Most importantly, the as-fabricated asymmetric supercapacitor, with a ZnO/Co3O4-450 positive electrode and an activated carbon negative electrode, delivered a prominent energy density of 47.7 W h kg–1 and a high power density of 7500 W kg–1. Thus, the ZnO/Co3O4 composites could serve as a high-activity material for supercapacitor and the preparation method also offers an attractive strategy to enhance the capacitive performance of Co3O4.
The history of China's municipal wastewater management is revisited. The remaining challenges in wastewater sector in China are identified. New concept municipal wastewater treatment plants are ...highlighted. An integrated plant of energy, water and fertilizer recovery is envisaged.
China has the world's largest and still growing wastewater sector and water market, thus its future development will have profound influence on the world. The high-speed development of China's wastewater sector over the past 40 years has forged its global leading treatment capacity and innovation ability. However, many problems were left behind, including underdeveloped sewers and sludge disposal facilities, low sustainability of the treatment processes, questionable wastewater treatment plant (WWTP) effluent discharge standards, and lacking global thinking on harmonious development between wastewater management, human society and the nature. Addressing these challenges calls for fundamental changes in target design, policy and technologies. In this mini-review, we revisit the development history of China's municipal wastewater management and identify the remaining challenges. Also, we highlight the future needs of sustainable development and exploring China's own wastewater management path, and outlook the future from several aspects including targets of wastewater management, policies and technologies, especially the new concept WWTP. Furthermore, we envisage the establishment of new-generation WWTPs with the vision of turning WWTP from a site of pollutant removal into a plant of energy, water and fertilizer recovery and an integrated part urban ecology in China.
Summary
Idiopathic multicentric Castleman disease (iMCD) is subclassified into iMCD‐thrombocytopenia, anasarca, reticulin fibrosis, renal dysfunction, organomegaly (TAFRO) and iMCD‐not otherwise ...specified (NOS) according to the Castleman Disease Collaborative Network (CDCN) consensus criteria. With a deeper understanding of iMCD, a group of patients with iMCD‐NOS characterised by polyclonal hypergammaglobulinaemia, plasmacytic/mixed‐type lymph node histopathology and thrombocytosis has attracted attention. This group of patients has been previously described as having idiopathic plasmacytic lymphadenopathy (IPL). Whether these patients should be excluded from the current classification system lacks sufficient evidence. This retrospective analysis of 228 patients with iMCD‐NOS identified 103 (45.2%) patients with iMCD‐IPL. The clinical features and outcomes of patients with iMCD‐IPL and iMCD‐NOS without IPL were compared. Patients with iMCD‐IPL showed a significantly higher inflammatory state but longer overall survival. No significant difference in overall survival was observed between severe and non‐severe patients in the iMCD‐IPL group according to the CDCN severity classification. Compared with lymphoma‐like treatments, multiple myeloma‐like and IL‐6‐blocking treatment approaches in the iMCD‐IPL group resulted in significantly higher response rates and longer time to the next treatment. These findings highlight the particularities of iMCD‐IPL and suggest that it should be considered a new subtype of iMCD‐NOS.
Idiopathic plasmacytic lymphadenopathy (IPL) was included as a part of idiopathic multicentric Castleman disease‐not otherwise specified (iMCD‐NOS) with hypergammaglobulinaemia, plasmacytic/mixed‐type lymph node histopathology and thrombocytosis. Patients with iMCD‐IPL present a significantly higher inflammatory state but longer overall survival. No significant difference in overall survival was observed between severe and non‐severe cases in the iMCD‐IPL group according to the Castleman Disease Collaborative Network (CDCN) severity classification. Compared with lymphoma‐like treatments, multiple myeloma‐like and IL‐6‐blocking treatment approaches in the iMCD‐IPL group resulted in significantly higher response rates and longer time to the next treatment. These findings highlight the particularities of iMCD‐IPL and suggest that it should be considered a new subtype of iMCD‐NOS.
High-performance and cost-effective electrocatalysts are essential for both oxygen evolution reaction (OER) and oxygen reduction reaction (ORR). Herein, we provide the first report about a facile ...colloidal method to fabricate 2D ultrathin ternary FeNiS2 nanosheets (NSs). When serving as an OER catalyst under alkaline conditions, they exhibited superior electrocatalytic performance over RuO2 and achieved a current density of 10mAcm−2 with a potential of 1.54V and a Tafel slope of 46mV decade−1. Meanwhile, an ORR catalytic activity was also achieved with an onset potential of 0.78V, a Tafel slope of 107mVdecade−1, and a high selectivity with electron transfer number of 3.92 and H2O2% of 3.6% at 0.3V under neutral conditions, which were comparable to those of the commercial Pt/C. The ternary FeNiS2-NSs were superior over the binary FeS NSs and Ni9S8 nanorods synthesized via the same routes. More importantly, with the resistance for the corrosion and poison from the alkaline and phosphate buffer solution, the FeNiS2 NSs exhibited superior stability without apparent OER or ORR catalytic activity loss over long-term operation. Their enhanced electrocatalytic performance compared to their binary counterparts indicate that a new strategy to prepare high performance OER and ORR catalysts was developed. In addition, the as-prepared FeNiS2 NSs could serve as a noble-metal-free catalyst for OER or ORR with good electrocatalytic activities and long-term stability for practical applications.
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•2D ternary FeNiS2 ultrathin nanosheet is synthesized using a facile colloidal method.•It exhibits excellent electrocatalytic activity and stability for both OER and ORR.•Its OER and ORR capacities are superior over binary FeS nanosheet and Ni9S8 nanorod.
Imidazole-based compounds are a series of heterocyclic compounds that exhibit a wide range of biological and pharmaceutical activities. However, those extant syntheses using conventional protocols ...can be time-costly, require harsh conditions, and result in low yields. As a novel and green technique, sonochemistry has emerged as a promising method for organic synthesis with several advantages over conventional methods, including enhancing reaction rates, improving yields, and reducing the use of hazardous solvents. Contemporarily, a growing body of ultrasound-assisted reactions have been applied in the preparation of imidazole derivatives, which demonstrated greater benefits and provided a new strategy. Herein, we introduce the brief history of sonochemistry and focus on the discussion of the multifarious approaches for the synthesis of imidazole-based compounds under ultrasonic irradiation and its advantages in comparison with conventional protocols, including typical name-reactions and various sorts of catalysts in those reactions.
Growing evidence points to the importance of cholesterol in preserving brain homeostasis. Cholesterol makes up the main component of myelin in the brain, and myelin integrity is vital in ...demyelinating diseases such as multiple sclerosis. Because of the connection between myelin and cholesterol, the interest in cholesterol in the central nervous system increased during the last decade. In this review, we provide a detailed overview on brain cholesterol metabolism in multiple sclerosis and its role in promoting oligodendrocyte precursor cell differentiation and remyelination.
•Myelin contains most of the cholesterol in the brain, and myelination is highly related to cholesterol metabolism.•Regulation of cholesterol metabolism has become a promising approach for the treatment of multiple sclerosis.•Dietary and modulators targeting cholesterol metabolism (Statins) promote OPC differentiation and remyelination.
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