Invertebrates rely on innate immunity, including humoral and cellular immunity, to resist pathogenic infection. Previous studies showed that forkhead box transcription factor O (FOXO) participates in ...mucosal immune responses of mammals and the gut humoral immune regulation of invertebrates. However, whether FOXO is involved in systemic and cellular immunity regulation in invertebrates remains unknown. In the present study, we identified a FOXO from shrimp (Marsupenaeus japonicus) and found that it was expressed at relatively basal levels in normal shrimp, but was upregulated significantly in shrimp challenged by Vibrio anguillarum. FOXO played a critical role in maintaining hemolymph and intestinal microbiota homeostasis by promoting the expression of Relish, the transcription factor of the immune deficiency (IMD) pathway for expression of antimicrobial peptides (AMPs) in shrimp. We also found that pathogen infection activated FOXO and induced its nuclear translocation by reducing serine/threonine kinase AKT activity. In the nucleus, activated FOXO directly regulated the expression of its target Amp and Relish genes against bacterial infection. Furthermore, FOXO was identified as being involved in cellular immunity by promoting the phagocytosis of hemocytes through upregulating the expression of the phagocytotic receptor scavenger receptor C (Src), and two small GTPases, Rab5 and Rab7, which are related to phagosome trafficking to the lysosome in the cytoplasm. Taken together, our results indicated that FOXO exerts its effects on homeostasis of hemolymph and the enteric microbiota by activating the IMD pathway in normal shrimp, and directly or indirectly promoting AMP expression and enhancing phagocytosis of hemocytes against pathogens in bacteria-infected shrimp. This study revealed the different functions of FOXO in the mucosal (local) and systemic antibacterial immunity of invertebrates.
Ternary approaches to solar cell design utilizing a small bandgap nonfullerene acceptor as the near infrared absorber to increase the short‐circuit current density always decreases the open‐circuit ...voltage. Herein, a highly efficient polymer solar cell with an impressive efficiency of 16.28 ± 0.20% enabled by an effective voltage‐increased ternary blended fullerene‐free material approach is reported. In this approach, the structural similarity between the host and the higher‐LUMO‐level guest enables the two acceptors to be synergized, obtaining increased open‐circuit voltage and fill factor and a small increase of short‐circuit current density. The same beneficial effects are demonstrated by using two host binary systems. The homogeneous fine film morphologies and the π–π stacking patterns of the host blend are well maintained, while larger donor and acceptor phases and increased lamellar crystallinity, increased charge mobilities, and reduced monomolecular recombination can be achieved upon addition of the guest nonfullerene acceptor. The increased charge mobilities and reduced monomolecular recombination not only contribute to the improved fill factor but also enable the best devices to be fabricated with a relatively thicker ternary blended active layer (110 vs 100 nm). This, combined with the absorption from the added guest acceptor, contribute to the increased short‐circuit current.
A ternary material system–enabled 16.5% efficiency fullerene‐free organic photovoltaic cell is designed with a structurally similar higher‐LUMO‐level guest nonfullerene acceptor. The homogeneous fine morphology and the π–π stacking pattern enable the two acceptors to synergize, obtaining increased open‐circuit voltage, short‐circuit current, and fill factor.
Background: Percutaneous radiofrequency ablation (RFA) is a first-line treatment for very-early-stage hepatocellular carcinoma (HCC), whereas the efficacy of percutaneous microwave ablation (MWA) for ...very-early-stage HCC remains unclear. The purpose of this study was to clarify this issue by comparing the safety and efficacy of percutaneous MWA with percutaneous RFA in treating very-early-stage HCC.Methods: Clinical data of 460 patients who were diagnosed with very-early-stage HCC and treated with percutaneous MWA or RFA between January 2007 and July 2012 at the Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, in Shanghai, China were retrospectively analyzed. Of these 460 patients, 159 received RFA, 301 received MWA. Overall survival (OS), recurrence-free survival (RFS), local tumor progression (LTP), complete ablation,and complication occurrence rates were compared between the two groups, and the prognostic factors associated with survival were analyzed.Results: No significant differences were observed between the two groups in terms of the 1-, 3-, or 5-year OS rates (99.3%, 90.4%, and 78.3% for MWA vs. 98.7%, 86.8%, and 73.3% for RFA, respectively; P = 0.331). Furthermore, no significant differences were observed between the two groups in terms of the corresponding RFS rates (94.4%, 71.8%, and 46.9% for MWA vs. 89.9%, 67.3%, and 54.9% for RFA, respectively; P = 0.309), the LTP rates (9.6% vs. 10.1%, P = 0.883),the complete ablation rates (98.3% vs. 98.1%, P = 0.860), or the occurrence rates of major complications (0.7% vs.0.6%, P = 0.691). By multivariate analysis, LTP, antiviral therapy, and treatment of recurrence were independent risk factors for OS (P < 0.001), and the alpha-fetoprotein level was an independent prognostic factor for RFS (P = 0.002).Conclusions: MWA is as safe and effective as RFA in treating very-early-stage HCC, supporting MWA as a first-line treatment option for this disease.
A visible‐light‐driven and room temperature photo‐Wolff‐Kischner reaction of sulfur ylides and N‐tosylhydrazones has been developed for the first time to provide modular access to alkene synthesis. ...The high functional group tolerance and broad substrate scope were demonstrated by more than 60 examples. Both E‐ and Z‐olefinic stereochemistry in the products could be controlled with excellent stereoselectivity. A series of mechanistic studies support that the reaction should proceed through a radical‐carbanion crossover pathway, specifically involving addition of photo‐generated sulfur ylide radical cations to N‐tosylhydrazones to form carbanions and subsequent Wolff‐Kischner process.
A visible‐light‐driven and room temperature photo‐Wolff–Kischner reaction of sulfur ylides and N‐tosylhydrazones has been developed for the first time to provide modular access to alkene synthesis. The high functional group tolerance and broad substrate scope were demonstrated by more than 60 examples. Both E‐ and Z‐olefinic stereochemistry in the products could be controlled with excellent stereoselectivity. A series of mechanistic studies support that the reaction should proceed through a radical‐carbanion crossover pathway. PC=photoredox catalysis. SET=single‐electron transfer.
Inflammatory depression is closely related to neuroinflammation. However, current anti-inflammatory drugs have low permeability to cross blood-brain barrier with difficulties reaching the central ...nervous system to provide therapeutic effectiveness. To overcome this limitation, the nano-based drug delivery technology was used to synthesize melanin-like polydopamine nanoparticles (PDA NPs) (~ 250 nm) which can cross the blood-brain barrier. Importantly, PDA NPs with abundant phenolic hydroxyl groups function as excellent free radical scavengers to attenuate cell damage caused by reactive oxygen species or acute inflammation. In vitro experiments revealed that PDA NPs exhibited excellent antioxidative properties. Next, we aimed to investigate the therapeutic effect of PDA NPs on inflammatory depression through intraperitoneal injection to the lipopolysaccharide-induced inflammatory depression model in mice. PDA NPs significantly reversed the depression-like behavior. PDA NPs was also found to reduce the peripheral and central inflammation induced by LPS, showing that alleviated splenomegaly, reduced serum inflammatory cytokines, inhibited microglial activation and restored synaptic loss. Various experiments also showed that PDA NPs had good biocompatibility both in vivo and in vitro. Our work suggested that PDA NPs may be biocompatible nano-drugs in treating inflammatory depression but their clinical application requires further study.
Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with extremely skewed ethnic and geographic distributions. Increasing evidence indicates that targeting the tumor microenvironment (TME) ...represents a promising therapeutic approach in NPC, highlighting an urgent need to deepen the understanding of the complex NPC TME. Here, we generated single-cell transcriptome profiles for 7581 malignant cells and 40,285 immune cells from fifteen primary NPC tumors and one normal sample. We revealed malignant signatures capturing intratumoral transcriptional heterogeneity and predicting aggressiveness of malignant cells. Diverse immune cell subtypes were identified, including novel subtypes such as CLEC9A
dendritic cells (DCs). We further revealed transcriptional regulators underlying immune cell diversity, and cell-cell interaction analyses highlighted promising immunotherapeutic targets in NPC. Moreover, we established the immune subtype-specific signatures, and demonstrated that the signatures of macrophages, plasmacytoid dendritic cells (pDCs), CLEC9A
DCs, natural killer (NK) cells, and plasma cells were significantly associated with improved survival outcomes in NPC. Taken together, our findings represent a unique resource providing in-depth insights into the cellular heterogeneity of NPC TME and highlight potential biomarkers for anticancer treatment and risk stratification, laying a new foundation for precision therapies in NPC.
Aims
Sevoflurane is widely used for general anesthesia in children. Previous studies reported that multiple neonatal exposures to sevoflurane can induce long‐term cognitive impairment in adolescent ...rats, but the underlying mechanisms were not defined.
Methods
Postnatal day 6 (P6) to P8 rat pups were exposed to 30% oxygen with or without 3% sevoflurane balanced with air. The Y maze test (YMT) and Morris water maze (MWM) tests were performed in some cohorts from age P35 to assess cognitive functions, and their brain samples were harvested at age P14, 21, 28, 35, and 42 for measurements of various molecular entities and in vivo electrophysiology experiments at age P35.
Results
Sevoflurane exposure resulted in cognitive impairment that was associated with decreased synCAM1 expression in parvalbumin (PV) interneurons, a reduction of PV phenotype, disturbed gamma oscillations, and dendritic spine loss in the hippocampal CA3 region. Enriched environment (EE) increased synCAM1 expression in the PV interneurons and attenuated sevoflurane‐induced cognitive impairment. The synCAM1 overexpression by the adeno‐associated virus vector in the hippocampal CA3 region restored sevoflurane‐induced cognitive impairment, PV phenotype loss, gamma oscillations decrease, and dendritic spine loss.
Conclusion
Our data suggested that neonatal sevoflurane exposure results in cognitive impairment through decreased synCAM1 expression in PV interneurons in the hippocampus.
Neonatal exposure to repeated sevoflurane anesthesia resulted in cognitive impairment associated with decreased synCAM1 expression in the hippocampal PV interneurons, reduced PV interneurons phenotype, and disturbed gamma oscillations. Moreover, overexpression of synCAM1 in the hippocampal PV interneurons improved cognitive function by restoring PV expression and gamma oscillations after repeated sevoflurane exposure.
•Prenatal urinary BPA and BPF exposures were associated with reduced birth length and increased ponderal index.•Prenatal urinary BPS exposure was associated with reduced gestational age.•Sex-specific ...associations of prenatal bisphenol exposures with fetal growth parameters were observed.
Bisphenol A (BPA) can cause detrimental effects on fetal growth. However, the effects of BPA alternatives, such as bisphenol F (BPF) and bisphenol S (BPS), on fetal growth are less known.
To investigate the relationships of prenatal BPA, BPF, and BPS exposures with fetal growth parameters and gestational age.
Urinary BPA, BPF, and BPS were measured in 1,197 pregnant women before delivery in a Chinese cohort. The associations of prenatal exposure to BPA, BPF, and BPS with fetal growth parameters and gestational age were examined, and associations stratified by fetal sex were also conducted. We used a restricted cubic splines (RCS) model to examine the dose–response associations between exposures and outcomes.
Maternal urinary BPA and BPF were negatively related to birth length (-0.30 cm, 95% CI: −0.44, −0.15 and −0.21 cm, 95% CI: −0.36, −0.07 comparing the extreme exposure groups, respectively, both p for trends < 0.01). These associations were more pronounced in girls with inverted U-shaped dose–response relationships. Maternal urinary BPA and BPF were positively related to ponderal index (0.05 g/cm3 × 100, 95% CI: 0.01, 0.09 and 0.04 g/cm3 × 100, 95% CI: 0.01, 0.08 comparing the extreme exposure groups, respectively, both p for trends = 0.02), and maternal urinary BPS was associated with shorter gestational age (-0.20 weeks, 95% CI: −0.37, −0.03 comparing the extreme exposure groups, p for trend = 0.02). These associations were only observed in girls and exhibited a linear dose–response relationship.
Prenatal BPA, BPF, and BPS exposures were associated with detrimental effects on fetal growth parameters, and stronger effects were noted in female infants.
This letter investigates a power allocation problem in a downlink single-input single-output non-orthogonal multiple access (NOMA) system. Our goal is to maximize the sum rate of users subject to ...minimum user rate requirements. We rigorously prove the optimal user decoding order, and show that the sum rate maximization problem is convex, which guarantees the globally optimal solution. Numerical results validate the performance gain by the proposed NOMA compared with conventional schemes.
During mammalian oocyte meiosis, spindle migration and asymmetric cytokinesis are unique steps for the successful polar body extrusion. The asymmetry defects of oocytes will lead to the failure of ...fertilization and embryo implantation. In present study, we reported that an actin nucleating factor Formin-like 2 (FMNL2) played critical roles in the regulation of spindle migration and organelle distribution in mouse and porcine oocytes. Our results showed that FMNL2 mainly localized at the oocyte cortex and periphery of spindle. Depletion of FMNL2 led to the failure of polar body extrusion and large polar bodies in oocytes. Live-cell imaging revealed that the spindle failed to migrate to the oocyte cortex, which caused polar body formation defects, and this might be due to the decreased polymerization of cytoplasmic actin by FMNL2 depletion in the oocytes of both mice and pigs. Furthermore, mass spectrometry analysis indicated that FMNL2 was associated with mitochondria and endoplasmic reticulum (ER)-related proteins, and FMNL2 depletion disrupted the function and distribution of mitochondria and ER, showing with decreased mitochondrial membrane potential and the occurrence of ER stress. Microinjecting
mRNA into FMNL2-depleted oocytes significantly rescued these defects. Thus, our results indicate that FMNL2 is essential for the actin assembly, which further involves into meiotic spindle migration and ER/mitochondria functions in mammalian oocytes.
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