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Background: Neonatal hyperoxia exposure is associated with brain injury and poor neurodevelopment outcomes in preterm infants. Our previous studies in neonatal rodent models have shown that hyperoxia stimulates the brain's inflammasome pathway, leading to the activation of gasdermin D (GSDMD), a key executor of pyroptotic inflammatory cell death. Moreover, we found pharmacological inhibition of caspase-1, which blocks GSDMD activation, attenuates hyperoxia-induced brain injury in neonatal mice. We hypothesized that GSDMD plays a pathogenic role in hyperoxia-induced neonatal brain injury and that GSDMD gene knockout (KO) will alleviate hyperoxia-induced brain injury. Methods: Newborn GSDMD knockout mice and their wildtype (WT) littermates were randomized within 24 h after birth to be exposed to room air or hyperoxia (85% O2) from postnatal days 1 to 14. Hippocampal brain inflammatory injury was assessed in brain sections by immunohistology for allograft inflammatory factor 1 (AIF1) and CD68, markers of microglial activation. Cell proliferation was evaluated by Ki-67 staining, and cell death was determined by TUNEL assay. RNA sequencing of the hippocampus was performed to identify the transcriptional effects of hyperoxia and GSDMD-KO, and qRT-PCR was performed to confirm some of the significantly regulated genes. Results: Hyperoxia-exposed WT mice had increased microglia consistent with activation, which was associated with decreased cell proliferation and increased cell death in the hippocampal area. Conversely, hyperoxia-exposed GSDMD-KO mice exhibited considerable resistance to hyperoxia as O2 exposure did not increase AIF1 + , CD68 + , or TUNEL + cell numbers or decrease cell proliferation. Hyperoxia exposure differentially regulated 258 genes in WT and only 16 in GSDMD-KO mice compared to room air-exposed WT and GSDMD-KO, respectively. Gene set enrichment analysis showed that in the WT brain, hyperoxia differentially regulated genes associated with neuronal and vascular development and differentiation, axonogenesis, glial cell differentiation, hypoxia-induced factor 1 pathway, and neuronal growth factor pathways. These changes were prevented by GSDMD-KO. Conclusions: GSDMD-KO alleviates hyperoxia-induced inflammatory injury, cell survival and death, and alterations of transcriptional gene expression of pathways involved in neuronal growth, development, and differentiation in the hippocampus of neonatal mice. This suggests that GSDMD plays a pathogenic role in preterm brain injury, and targeting GSDMD may be beneficial in preventing and treating brain injury and poor neurodevelopmental outcomes in preterm infants. [ABSTRACT FROM AUTHOR]

Background: Hypoxia is a very common adverse event that occurs during gastrointestinal endoscopy under sedation, especially in older patients, owing to limited reservation of heart, brain, lung, and other organs. Prolonged or severe hypoxia can cause ischemia of the coronary artery and permanent nervous system damage, and even result in death. Hence, it is imperative to reduce or prevent hypoxia during gastrointestinal endoscopy under sedation in older patients. Although several oxygen delivery methods would reduce hypoxia during this procedure, early detection of respiratory depression and early administration of intervention would be the best method to reduce or even confirm the hypoxia. Capnographic monitoring is reportedly more sensitive for detecting respiratory depression before the onset of hypoxia than the current clinical routine monitoring of pulse oxygen saturation; however, its effect is controversial. Therefore, in this study, we aimed to improve the safety of gastrointestinal endoscopy under sedation in older patients. Methods: A multicenter, randomized, single-blind, two-arm parallel-group, controlled with an active comparator, interventional superiority clinical trial will be conducted to evaluate the impact of an additional capnographic monitoring-based intervention on the incidence of hypoxia in older patients. Patients (n = 1800) scheduled for gastrointestinal endoscopy with propofol sedation will be randomly assigned to either a control or interventional arm, wherein standard or capnographic monitoring is implemented, respectively. Discussion: This study primarily aims to examine whether an additional capnographic monitoring-based intervention can reduce the incidence of hypoxia in older patients during gastrointestinal endoscopy under propofol and sufentanil sedation. The results of this study may extensively impact gastrointestinal endoscopy under sedation and the development of associated guidelines. Trial registration: ClinicalTrials.gov NCT05030870. Registered on September 1, 2021. [ABSTRACT FROM AUTHOR]

Antibodies and antigen-binding fragments (Fabs) can be used to modify the surface of nanoparticles for enhanced target binding. In our previous work, site-specific conjugation of Fabs to polymeric micelles using conventional methods was limited to approximately 30% efficiency, possibly due to steric hindrance related to macromolecular reactants. Here, we report a new method that enables conjugation of Fabs onto a micelle surface in a controlled manner with up to quantitative conversion of nanoparticle reactive groups. Variation of (i) PEG spacer length in a heterofunctionalized cross-linker and (ii) Fab/polymer feed ratios resulted in production of nanoparticles with a range of Fab densities on the surface up to the theoretical maximum value. The biological impact of variable Fab density was evaluated in vitro with respect to cell uptake and cytotoxicity of a drug-loaded (SN38) targeted polymeric micelle bearing anti-EphA2 Fabs. Fab conjugation increased cell uptake and potency compared with non-targeted micelles, although a Fab density of 60% resulted in decreased uptake and potency of the targeted micelles. Altogether, our findings demonstrate that conjugation strategies can be optimized to allow control of Fab density on the surface of nanoparticles and also that Fab density may need to be optimized for a given cell-surface target to achieve the highest bioactivity. [ABSTRACT FROM AUTHOR]

Antibodies and antigen-binding fragments (Fabs) can be used to modify the surface of nanoparticles for enhanced target binding. In our previous work, site-specific conjugation of Fabs to polymeric micelles using conventional methods was limited to approximately 30% efficiency, possibly due to steric hindrance related to macromolecular reactants. Here, we report a new method that enables conjugation of Fabs onto a micelle surface in a controlled manner with up to quantitative conversion of nanoparticle reactive groups. Variation of (i) PEG spacer length in a heterofunctionalized cross-linker and (ii) Fab/polymer feed ratios resulted in production of nanoparticles with a range of Fab densities on the surface up to the theoretical maximum value. The biological impact of variable Fab density was evaluatedin vitrowith respect to cell uptake and cytotoxicity of a drug-loaded (SN38) targeted polymeric micelle bearing anti-EphA2 Fabs. Fab conjugation increased cell uptake and potency compared with non-targeted micelles, although a Fab density of 60% resulted in decreased uptake and potency of the targeted micelles. Altogether, our findings demonstrate that conjugation strategies can be optimized to allow control of Fab density on the surface of nanoparticles and also that Fab density may need to be optimized for a given cell-surface target to achieve the highest bioactivity. [ABSTRACT FROM AUTHOR]

Emerging integrated CPU + FPGA hybrid platforms, such as the Extensible Processing Platform architecture from Xilinx [1] , offer unprecedented opportunity to achieving both multifunctionality and real-time responsiveness for memory-intensive embedded applications. However, how to cost-effectively synthesize application-specific hardware constructs that fully exploit memory-level parallelism remains to be a key challenge. To address this problem, we propose a new FPGA-based embedded computer architecture, ASTRO (Application-Specific Hardware Traces with Reconfigurable Optimization). Our main contribution is the development of an integrated methodology that focuses on how to construct an application-specific memory access network capable of extracting the maximum amount of memory-level parallelism on a per-application basis. In particular, our proposed ASTRO architecture can (1) perform dynamic memory analysis to maximally extract the target application’s instruction, loop and memory-level parallelism for performance enhancement, (2) synthesize highly efficient accelerators that enable parallelized memory accesses, and therefore (3) accomplish effective data orchestration by utilizing the capabilities of modern FPGA devices: abundant distributed block RAMs and reprogrammability. To empirically validate our ASTRO methodology, we have implemented a baseline embedded processor platform, a conventional CPU + accelerator with a centralized single memory, and a prototype ASTRO machine based on Xilinx MicroBlaze technology. Our experimental results show that on average for 10 benchmark applications from SPEC2006 and MiBench [2] , the ASTRO machine achieves 8.6 times speedup compared to the baseline embedded processor platform and 1.7 times speedup compared to a conventional CPU + accelerator platform. More interestingly, the ASTRO platform achieves more than 40% reduction in energy-delay product compared to a conventional CPU + accelerator with a centralized memory. [ABSTRACT FROM AUTHOR]

Heavy metal contamination in soils has been a severe issue in agricultural production around the world in the past few decades because of its high health risk through soil-food chain transfer. A sudden emergence of heavy metal tainted rice from the South China market urged countermeasures to prevent heavy metal uptake and accumulation in rice from heavy metal contaminated rice paddies. To investigate and quantify the effects of combined application of biochar (BC) and nitrogen fertilizers on the growth, yield and heavy metal uptake of rice (Oryza sativa L.) on a historically multi-metal contaminated paddy soil, the pot experiments under waterlogged condition were carried out in a greenhouse and five different treatments were compared including control soil, soil only with common nitrogen fertilizer ammonium sulphate nitrate (ASN), soil only with nitrogen fertilizer ammonium sulphate nitrate with nitrification inhibitor 3,4-dimethylpyrazolephosphate (DMPP), soil both with biochar and common nitrogen fertilizer, and soil both with biochar and DMPP nitrogen fertilizer. Both soil and rice plant samples were collected after rice harvest. Available heavy metals of soils, roots, straws and grains of rice were analyzed. The results showed that nitrogen fertilizer with nitrification inhibitor DMPP had no significant (P>0.05) effect on rice grain yield if they were not used in combination with biochar. Biochar combined with common nitrogen fertilizer or DMPP nitrogen fertilizer could significantly (P<0.05) increased the grain yield. Compared with the single application of common nitrogen fertilizer, the grain yield of rice in the treatment with combined use of biochar and common nitrogen fertilizer was significantly (P<0.05) increased by 20.3%. Compared with the single application of DMPP nitrogen fertilizer, the grain yield of rice in the treatment with combined use of biochar and DMPP nitrogen fertilizer was significantly (P<0.05) increased by 49.3%. Compared with the control, the concentrations of Cu, Zn and Cd in grain of in the treatment with combined use of biochar and DMPP nitrogen fertilizer were significantly (P<0.05) decreased by 20.0%, 21.4% and 11.6%, respectively. DMPP could promote the transfer of Cu from straw to grain when biochar was not applied together, but promote the transfer of Cu and Cd from root to straw when biochar was used together. The effect of combined application of biochar and nitrogen fertilizer on transfer of Cu and Cd varied with different nitrogen fertilizer. The results above indicated that combined application of biochar and DMPP nitrogen fertilizer could promote rice growth, increase the yields of rice grain and decrease its heavy metal Cu, Zn and Cd concentrations. The results further suggested that in a multi-contaminated watterlogged paddy soil, biochar and DMPP nitrogen fertilizer could be adopted together. This study demonstrated the application of both biochar and DMPP nitrogen fertilizer could prevent dangerous heavy metal accumulation in heavy metal contaminated paddy field. [ABSTRACT FROM AUTHOR]

Bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) are among the most common morbidities affecting extremely premature infants who receive oxygen therapy. Many clinical studies indicate that BPD is associated with advanced ROP. However, the mechanistic link between hyperoxia, BPD, and ROP remains to be explored. Gasdermin D (GSDMD) is a key executor of inflammasome-induced pyroptosis and inflammation. Inhibition of GSDMD has been shown to attenuate hyperoxia-induced BPD and brain injury in neonatal mice. The objective of this study was to further define the mechanistic roles of GSDMD in the pathogenesis of hyperoxia-induced BPD and ROP in mouse models. Here we show that global GSDMD knockout (GSDMD-KO) protects against hyperoxia-induced BPD by reducing macrophage infiltration, improving alveolarization and vascular development, and decreasing cell death. In addition, GSDMD deficiency prevented hyperoxia-induced ROP by reducing vasoobliteration and neovascularization, improving thinning of multiple retinal tissue layers, and decreasing microglial activation. RNA sequencing analyses of lungs and retinas showed that similar genes, including those from inflammatory, cell death, tissue remodeling, and tissue and vascular developmental signaling pathways, were induced by hyperoxia and impacted by GSDMD-KO in both models. These data highlight the importance of GSDMD in the pathogenesis of BPD and ROP and suggest that targeting GSDMD may be beneficial in preventing and treating BPD and ROP in premature infants. [ABSTRACT FROM AUTHOR]

Background: Mechanical ventilation of preterm newborns causes lung injury and is associated with poor neurodevelopmental outcomes. However, the mechanistic links between ventilation-induced lung injury (VILI) and brain injury is not well defined. Since circulating extracellular vesicles (EVs) are known to link distant organs by transferring their cargos, we hypothesized that EVs mediate inflammatory brain injury associated with VILI.Methods: Neonatal rats were mechanically ventilated with low (10 mL/kg) or high (25 mL/kg) tidal volume for 1 h on post-natal day 7 followed by recovery for 2 weeks. Exosomes were isolated from the plasma of these rats and adoptively transferred into normal newborn rats. We assessed the effect of mechanical ventilation or exosome transfer on brain inflammation and activation of the pyroptosis pathway by western blot and histology.Results: Injurious mechanical ventilation induced similar markers of inflammation and pyroptosis, such as increased IL-1β and activated caspase-1/gasdermin D (GSDMD) in both lung and brain, in addition to inducing microglial activation and cell death in the brain. Isolated EVs were enriched for the exosomal markers CD9 and CD81, suggesting enrichment for exosomes. EVs isolated from neonatal rats with VILI had increased caspase-1 but not GSDMD. Adoptive transfer of these EVs led to neuroinflammation with microglial activation and activation of caspase-1 and GSDMD in the brain similar to that observed in neonatal rats that were mechanically ventilated.Conclusions: These findings suggest that circulating EVs can contribute to the brain injury and poor neurodevelopmental outcomes in preterm infants with VILI through activation of GSDMD. [ABSTRACT FROM AUTHOR]

The development of tumor-targeting nanocarriers is critical important for effective treatment. The synthetic polyesters have demonstrated high potential for developing nanocarriers for cancer theranostics. Especially, the biocompatible and biodegradable polyester micelles have held great promise for cancer therapy and diagnosis, while some candidates have been translated into clinical applications or under clinical trial. In this review, we have provided the state-of-the-art of polyester micelles for drug delivery and cancer theranostics. In addition, we have summarized several major types of polyesters used in the biomedical fields, the current clinical achievements of polyester micelles and recent progresses of multi-functional polyester micelles for tumor molecular imaging and therapeutic applications. [ABSTRACT FROM AUTHOR]

This paper describes the fate of a nitrobenzene-degrading bacterium, Klebsiella oxytoca NBA-1, which was isolated from a pharmaceutical wastewater treatment facility. The 90-day survivability of strain NBA-1 after exposure to sludge under anaerobic and aerobic conditions was investigated. The bacterium was inoculated into sludge amended with glucose and p -chloronitrobenzene ( p -CNB) to compare the bacterial community variations between the modified sludge and nitrobenzene amendment. The results showed that glucose had no obvious effect on nitrobenzene biodegradation in the co-metabolism process, regardless of the presence/absence of oxygen. When p -CNB was added under anaerobic conditions, the biodegradation rate of nitrobenzene remained unchanged although p -CNB inhibited the production of aniline. The diversity of the microbial community increased and NBA-1 continued to be one of the dominant strains. Under aerobic conditions, the degradation rate of both nitrobenzene and p -CNB was only 20% of that under anaerobic conditions. p -CNB had a toxic effect on the microorganisms in the sludge so that most of the DGGE (denaturing gradient gel electrophoresis) bands, including that of NBA-1, began to disappear under aerobic conditions after 90 days of exposure. These data show that the bacterial community was stable under anaerobic conditions and the microorganisms, including NBA-1, were more resistant to the adverse environment. [ABSTRACT FROM AUTHOR]

Hyperoxia-induced lung injury plays a key role in the development of bronchopulmonary dysplasia (BPD), characterized by inflammatory injury and impaired lung development in preterm infants. Although BPD is a predictor of poor neurodevelopmental outcomes, currently it is uncertain how lung injury contributes to brain injury in preterm infants. Extracellular vesicles (EVs) are a heterogeneous group of cell-derived membranous structures that regulate intercellular and inter-organ communications. Gasdermin D (GSDMD) has emerged as a key executor of inflammasome-mediated cell death and inflammation. In this study, we utilized a neonatal rat model of BPD to assess if hyperoxia stimulates lung release of circulating EVs and if these EVs induce lung and brain injury. We found that hyperoxia-exposed rats had elevated numbers of plasma-derived EVs compared to rats maintained in room air. These EVs also had increased cargos of surfactant protein C, a marker of type II alveolar epithelial cells (AEC), and the active (p30) form of GSDMD. When these EVs were adoptively transferred into normal newborn rats via intravenous injection, they were taken up both by lung and brain tissues. Moreover, EVs from hyperoxic animals induced not only the pathological hallmarks of BPD, but also brain inflammatory injury in recipient rats, as well as inducing cell death in cultured pulmonary vascular endothelial cells and neural stem cells (NSC). Similarly, hyperoxia-exposed cultured AEC-like cells released EVs that also contained increased GSDMD-p30 and these EVs induced pyroptotic cell death in NSC. Overall, these data indicate that hyperoxia-activated circulating EVs mediate a lung to brain crosstalk resulting in brain injury and suggest a mechanism that links lung injury and neurodevelopmental impairment in BPD infants. [ABSTRACT FROM AUTHOR]

Background: Photodynamic therapy (PDT) can be performed as palliative therapy for cholangiocarcinoma, while there is currently insufficient evidence for the efficacy. The aim of this study was to explore the clinical efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP)- or percutaneous transhepatic cholangioscopy (PTCS)-directed PDT combined with stent placement for unresectable hilar cholangiocarcinoma. Methods: A retrospective analysis was conducted on 62 patients with unresectable hilar cholangiocarcinoma. Thirty patients received PDT using hematoporphyrin combined with biliary stent placement (PDT+stent group), including 22 receiving ERCP-directed PDT and 8 receiving PTCS-directed PDT. Survival time, quality of life, and postoperative adverse events were compared to 32 patients receiving biliary stent placement alone (Stent-only group). Results: After 42 months of follow-up, median survival time was significantly longer in the PDT+stent group than the Stent-only group (14.2 vs. 9.8 months, P = 0.003). In the PDT+stent group, the median survival time was longer in the 6 patients with recurrence after surgical resection than the 24 patients without prior surgical resection (20.0 vs. 13.0 months, P = 0.017). The QOL total scores was significantly higher in the PDT+stent group than the Stent-only group at postoperative 6, 9, and 12 months (P<0.05). There was no significant difference in the incidence of postoperative adverse events between the two groups (24 [38.7%] vs. 20 [29.0%], P = 0.239). Conclusion: ERCP- or PTCS-directed PDT + stent placement can prolong the survival of patients with unresectable hilar cholangiocarcinoma, especially those with recurrence and improve quality of life without increasing adverse events. [ABSTRACT FROM AUTHOR]

Hyperoxia-induced lung injury plays a key role in the development of bronchopulmonary dysplasia (BPD), characterized by inflammatory injury and impaired lung development in preterm infants. Although BPD is a predictor of poor neurodevelopmental outcomes, currently it is uncertain how lung injury contributes to brain injury in preterm infants. Extracellular vesicles (EVs) are a heterogeneous group of cell-derived membranous structures that regulate intercellular and inter-organ communications. Gasdermin D (GSDMD) has emerged as a key executor of inflammasome-mediated cell death and inflammation. In this study, we utilized a neonatal rat model of BPD to assess if hyperoxia stimulates lung release of circulating EVs and if these EVs induce lung and brain injury. We found that hyperoxia-exposed rats had elevated numbers of plasma-derived EVs compared to rats maintained in room air. These EVs also had increased cargos of surfactant protein C, a marker of type II alveolar epithelial cells (AEC), and the active (p30) form of GSDMD. When these EVs were adoptively transferred into normal newborn rats via intravenous injection, they were taken up both by lung and brain tissues. Moreover, EVs from hyperoxic animals induced not only the pathological hallmarks of BPD, but also brain inflammatory injury in recipient rats, as well as inducing cell death in cultured pulmonary vascular endothelial cells and neural stem cells (NSC). Similarly, hyperoxia-exposed cultured AEC-like cells released EVs that also contained increased GSDMD-p30 and these EVs induced pyroptotic cell death in NSC. Overall, these data indicate that hyperoxia-activated circulating EVs mediate a lung to brain crosstalk resulting in brain injury and suggest a mechanism that links lung injury and neurodevelopmental impairment in BPD infants. [ABSTRACT FROM AUTHOR]

A novel (NH4)2Mo4O13/N-doped porous carbon composite is fabricated in situ using a one-step solid technique. Benefiting from the intriguing features of this composite, it undergoes an intercalation and conversion reaction mechanism with diffusion-controlled Li storage behaviour, exhibiting an excellent reversible capacity of 1151 mA h g−1 over 350 cycles. [ABSTRACT FROM AUTHOR]

Self-assembled cactus-like NH 4 V 3 O 8 is prepared through polyethylene glycol (PEG)-assisted hydrothermal synthesis method. The samples are characterized by X-ray diffraction and scanning electron microscopy techniques. Adjusting the pH value of the solution can effectively control the morphology of NH 4 V 3 O 8. The electrochemical measurements indicate that the sample which pH value is 3.7, shows the best cycling performance. It delivers an initial discharge capacity is 228 mAh g−1 and maintains at 156 mAh g−1 under 15 mA g−1 after 50 cycles. The proposed synthetic method can also be developed to address other electrode materials with inferior electronic conductivity and lithium ion diffusion. Schematic illustration of cactus-like NH 4 V 3 O 8 by PEG4000-assisted hydrothermal method Image, graphical abstract [ABSTRACT FROM AUTHOR]

Summary: Ferrous sulfides have high theoretical capacity in the electrochemical storage of Na‐ion and K‐ion, but its obvious volume change during the storage process greatly affects its cycling performance at high current density. In this regard, we construct a unique composites structure of Nitrogen‐doped carbon shell coated FeS nanoparticle with inner void spaces. As an anode in Na‐ion and K‐ion batteries, this structure could provide excellent cycling performance at high rate of charge/discharge process (560 mAh/g at 0.5 A/g for 300 cycles in Na‐ion battery and 322 mAh/g at 1 A/g for 300 cycles in K‐ion battery). Further research finds the inner void space could not only provide buffer space for the volume change of FeS nanoparticles, but also maintain a stable outer carbon shell during the electrochemical process. These behaviors greatly promote the reversibility of FeS at high rate charge transfer process. Consequently, the construction of inner void space in graphitized carbon shell in this work could be considered as an important reference for the promotion of electrochemical storage in other transitional metal compound system. [ABSTRACT FROM AUTHOR]

Background: Inflammatory injury, particularly the production of active interleukin (IL)-1β plays a major role in the pathogenesis of bronchopulmonary dysplasia (BPD) in preterm infants. The release of active IL-1β is controlled by posttranscriptional modifications of its proform (pro-IL-1β) through the inflammasome. Rac1 is a member of the Rho family of GTPases that regulate the inflammatory process. Objective: This study tested the hypothesis that Rac1 signaling increases inflammasome activation that results in damaging inflammation, and that the inhibition of Rac1 signaling prevents lung injury, by inhibiting inflammasome activation in a newborn rat model of BPD induced by hyperoxia. Methods: Newborn rat pups were exposed to room air or hyperoxia (85% O2) and received daily intraperitoneal injections of placebo (normal saline) or NSC23766, a specific Rac1 inhibitor, for 10 days. The effects on lung inflammation, alveolarization, vascular development, vascular remodeling, right ventricular systolic pressure, and right ventricular hypertrophy (RVH) were then assessed. Results: Hyperoxia exposure upregulated Rac1 and increased the production of active IL- 1β, which was accompanied by increasing expression of the inflammasome. In addition, hyperoxia induced the pathological hallmarks of BPD. However, treatment with NSC23766 significantly decreased inflammasome activation and macrophage infiltration, improved alveolar and vascular development, and reduced pulmonary vascular remodeling and RVH. Conclusion: These results indicate that Rac1 signaling regulates the expression of the inflammasome and plays a pivotal role in the pathogenesis of hyperoxia-induced neonatal lung injury. Therefore, targeting Rac1 signaling may provide a novel strategy to prevent and treat BPD in preterm infants. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) play a dual role in tumors. However, the factors which drive the function of TAMs in cholangiocarcinoma remain largely undefined. SHH signaling pathway and endoplasmic reticulum stress (ERS) indicators were detected in clinical tissues and cholangiocarcinoma cell lines. TAMs were co-cultured with cholangiocarcinoma cells under conditions of hypoxia/normoxia. Polarized TAMs were counted by flow cytometry, and TGF-β1 levels in cell supernatants were detected by ELISA. The effects of glioma-associated oncogene GLI2 on TAMs themselves and cholangiocarcinoma cells were examined by conducting interference and overexpression assays. The SHH signaling pathway and ERS were both activated in tumor tissues or tumor cell lines under conditions of hypoxia. In co-culture experiments, the presence of cholangiocarcinoma cells increased the proportion of M2-polarized TAMs and the secretion of TGF-β1 by TAMs, while knockdown of SHH expression reversed those increases. Overexpression of GLI2 in TAMS or stimulation of TAMS with Hh-Ag1.5 increased their levels of TGF-β1 expression. Furthermore, under co-culture conditions, interference with GLI2 expression in TAMs reduced the tumor cell migration, invasion, and ER homeostasis induced by Hh-Ag1.5-pretreated TAMs. Under conditions of hypoxia, the presence of cholangiocarcinoma cells promoted the expression of GLI2 and TGF-β1 in Tams, and in turn, TAMs inhibited the apoptosis and promoted the migration and invasion of cholangiocarcinoma cells. In vivo, an injection of cholangiocarcinoma cells plus TAMs contributed to the growth, EMT, and ER homeostasis of tumor tissue, while an injection of TAMs with GLI2 knockdown had the opposite effects. Cholangiocarcinoma cells regulated TAM polarization and TGF-β1 secretion via a paracrine SHH signaling pathway, and in turn, TAMs promoted the growth, EMT, and ER homeostasis of cholangiocarcinoma cells via TGF-β1. [Display omitted] • Hypoxia increases SHH level in tumor microenvironment. • Cancer cell derived SHH modulates TAMs polarization and promotes transcriptional expression of TGF-β1. • TGF-β1 secreted by TAMs further activates SHH/GLI2 signaling in cholangiocarcinoma cells. • SHH/GLI2-TGF-β1 loop maintains epithelial-mesenchymal transition and endoplasmic reticulum homeostasis in cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Post-operative cognitive dysfunction (POCD) is an overarching term used to describe cognitive impairment identified in the preoperative or post-operative period. After surgical operations, older patients are particularly vulnerable to memory disturbances and other types of cognitive impairment. However, the pathogenesis of POCD remains unclear with no confirmed preventable or treatable strategy available. Our previous study demonstrated that the concentration of choline acetyl transferase in the cerebral spinal fluid was a predictive factor of POCD and that donepezil, which is an acetylcholinesterase inhibitor used in clinical settings for the treatment of Alzheimer's disease, can prevent learning and memory impairment after anaesthesia/surgery in aged mice. This study aimed to determine the critical role of donepezil in preventing cognitive impairment in elderly patients undergoing orthopaedic surgery.Methods: A multicentre, double-blind, placebo-controlled, crossover clinical trial will be performed to assess the efficacy of donepezil in elderly patients undergoing orthopaedic surgery. Participants (n = 360) will receive donepezil (5 mg once daily) or placebo from 1 day prior to surgery until 5 days after surgery. Neuropsychological tests will be measured at 1 day before the operation and 1 week, 1 month, 6 months and 1 year after the operation.Discussion: This research project mainly aimed to study the effects of donepezil in elderly patients undergoing orthopaedic surgery due to underlying POCD and to investigate the underlying physiological and neurobiological mechanisms of these effects. The results may provide important implications for the development of effective interfering strategies, specifically regarding cognitive dysfunction therapy using drugs.Trial Registration: ClinicalTrials.gov NCT04423276 . Registered on 14 June 2020. [ABSTRACT FROM AUTHOR]

"The authors declare no competing interests." now reads: "JPdRV, WDD and RWK are co-founders and managing members of InflamaCORE, LLC and have licensed patents on inflammasome proteins as biomarkers of injury and disease as well as on targeting inflammasome proteins for therapeutic purposes. JPdRV, WDD and RWK are Scientific Advisory Board Members of ZyVersa Therapeutics.". [Extracted from the article]

Traumatic brain injury (TBI) results in significant hippocampal pathology and hippocampal-dependent memory loss, both of which are alleviated by hypothermia treatment. To elucidate the molecular mechanisms regulated by hypothermia after TBI, rats underwent moderate parasagittal fluid-percussion brain injury. Brain temperature was maintained at normothermic or hypothermic temperatures for 30 min prior and up to 4 h after TBI. The ipsilateral hippocampus was assayed with Western blotting. We found that hypothermia potentiated extracellular signal-regulated kinase 1/2 (ERK1/2) activation and its downstream effectors, p90 ribosomal S6 kinase (p90RSK) and the transcription factor cAMP response element-binding protein. Phosphorylation of another p90RSK substrate, Bad, also increased with hypothermia after TBI. ERK1/2 regulates mRNA translation through phosphorylation of mitogen-activated protein kinase-interacting kinase 1 (Mnk1) and the translation factor eukaryotic initiation factor 4E (eIF4E). Hypothermia also potentiated the phosphorylation of both Mnk1 and eIF4E. Augmentation of ERK1/2 activation and its downstream signalling components may be one molecular mechanism that hypothermia treatment elicits to improve functional outcome after TBI. [ABSTRACT FROM AUTHOR]

Increasing evidence indicates the adverse effect of air pollution exposure during pregnancy on neurologic development among children. However, the impact on neurobehavioral development in fetus remains unknown. In 2017, a total of 1193 mother–newborns pairs were enrolled in a birth cohort study in Changsha, China. Exposures to PM 2.5 , PM 10, SO 2 , CO and NO 2 were determined by using inverse distance weighted method based on local monitoring station data. Neurobehavioral measure was administered at 48–72 h postpartum by utilizing the neonatal behavioral neurological assessment (NBNA). Basic information and covariates were collected by face to face interview. Generalized linear regression and multivariable restricted cubic spline function were performed to explore the trimester-specific association and dose-response relationship of maternal air pollution exposure with NBNA score, respectively. In adjusted three-pollutant model, PM 2.5 exposure in trimester 2 was negatively associated with behavior score (β, −0.003; 95% CI, −0.006, −0.001) and the inverse relation was more pronounced in male infants. In addition, PM 2.5 level in the 2nd trimester was negatively related to activetone score (β, −0.012; 95% CI, −0.021, −0.002) in a dose-dependent manner for both genders. Collectively, our results demonstrated that prenatal exposure to PM 2.5 was linked to poor neurobehavioral performance of newborns. The second trimester was the most sensitive time window for the developments of behavior and activetone, and male subject was more vulnerable as compared to females. • Prenatal exposure to PM 2.5 was associated with poor neurobehavioral performance of newborns. • The second trimester was the most sensitive time window for behavioral and activetone development. • Male newborns were more vulnerable to the influence of PM 2.5 as compared to females. [ABSTRACT FROM AUTHOR]

• A core–shell structure polypyrrole coated Cu/Cu 2 O nanowires was synthesized. • Li-storage performance of Cu 2 O can be enhanced by introduction of Cu metal and Ppy. • The high capacity of 401 mAh g−1 is still delivered at 1 Ag−1 after 500 cycles. • A phase transformation is proved to be the main reasons for capacity increase. A core-shell structure polypyrrole coated Cu/Cu 2 O (Cu/Cu 2 O@Ppy) nanowires was synthesized by a facile hydrothermal method. Benefiting from the nanowire morphology, the confinement effect of Ppy shell and the modification of Cu metal, the Cu/Cu 2 O@Ppy as the anode of lithium ion battery exhibits an increased reversible capacity of 787 mAh g−1 under the current density of 0.1 A g−1 after 250 cycles. In addition, a good long-life rate capacity also can be obtained (401 mAh g−1 at 1 A g−1 after 500 cycles). More to the point, the increased capacity of Cu/Cu 2 O@Ppy nanowires is explained by the analysis of capacity differential curve, ex-situ X-ray photoelectron spectroscopy and electrochemical impedance spectroscopy. It was demonstrated that the constant formation of solid electrolyte interface film and the transformation of Cu to Cu 2 O lead to the increased capacity in the initial cycles. Furthermore, a phase transformation of host material from Cu 2 O to CuO is proved to be the main reasons for the subsequent cycles of capacity increase. This in-situ phase transformation of electrode material provides a novel perspective for the increased capacity phenomenon of metal compounds in lithium ion battery. [ABSTRACT FROM AUTHOR]

• Fe 2 O 3 "mulberry" architecture, quantum dots and bulk particles were synthesized. • Dominant pseudocapacitive feature of the assembled render fast ionic storage. • Less SEI on surface enables the assembled to realize high coulombic efficiency. Constructing pseudocapacitive materials to combine the battery-level energy density with the cycle life and power density of supercapacitors is a promising energy storage technique. Nanostructuring can greatly induce extrinsic pseudocapacitance, but excessive solid electrolyte interphase (SEI) as the activity surface increases usually results in a poor coulombic efficiency (CE) of battery. Here, we separately investigate the electrochemical properties of self-assembled Fe 2 O 3 "mulberry" architecture, quantum dots and bulk particles. Employed as an anode of lithium ion battery, the mulberry architecture retains a dominant pseudocapacitance behavior and high electrochemical activity. It delivers an initial capacity of 1383.8 mAh g−1, 22.1% higher than Fe 2 O 3 bulk in similar size, in which the pseudocapacitance contribution up to 80.6% at 0.4 mV s−1. Furthermore, the mulberry architecture decreases the activity surface contacted with electrolyte to enable a limited SEI, achieving a higher coulombic efficiency (initial CE: 80.1%, average CE: 98.9%) well above that of individual quantum dots. This work is expected to inspire the design of novel high-performance anode materials. [ABSTRACT FROM AUTHOR]

Development of three-dimensional self-assembled hollow nanoarchitectures combining functional shells and inner voids is an important approach for realizing high-rate and long-life battery electrodes. As a potential high-performance anode for sodium-ion batteries (SIBs), (1 1 0)-bridged nanoblocks self-assembled VS 4 hollow microspheres (PNBH-VS 4) are controllably synthesized by a facile one-step hydrothermal method. The (1 1 0)-bridged structure constructs the Na+ conducting channels and e− transfer paths among nano-grains and nanoblocks, and the self-assembled hollow structure presents the double space physical entrapment effect for the excessive volume change of nanoblocks, which synergistically improve the Na+ storage kinetics and structure stability. When employed as an anode for SIBs, PNBH-VS 4 electrode exhibits the superior rate capability and long cycling life, outperforming those of the ever-reported VS 4 -based anode materials. At 0.2, 0.5, 1.0 and 2.0 A g−1, the capacity can reach 629, 564, 428 and 400 mAh g−1 after 250, 200, 350 and 700 cycles, respectively. Even at 5.0 A g−1, the capacity can still stabilize at 309 mAh g−1 after 1000 long cycles. In addition, it is revealed that PNBH-VS 4 electrode undertakes the insertion and conversion reaction in the potential range of 0.50–3.00 and 0.05–0.50 V, respectively, where the main capacity contribution originates from the insertion reaction. Meanwhile, PNBH-VS 4 electrode exhibits better insertion reversibility at lower current densities and conversion reversibility at higher current densities during cycling, respectively. [ABSTRACT FROM AUTHOR]

Porous carbon anodes are widely used for sodium-ion batteries storage, sodium-ion insertion/extraction in porous carbon anodes always accompanies with exfoliation/accumulation of carbon sheets. Whether exfoliation/accumulation of carbon sheets has influence on sodium storage is still unknown. We control alkali activation concentration to form porous carbon sheets with different etching degrees. Results show the etching degree is decided by exfoliation/accumulation rate of porous carbon sheets. When sodium ions insert into carbon sheets, carbon sheets with lower etching degree begin to exfoliate and carbon sheets with higher etching degree start to accumulate. As the current density increases, accumulation/exfoliation process alternates and repeats ceaselessly. The number of exposed inner defects near pores changes during electrochemical reaction process, which is caused by accumulating/exfoliating of carbon sheets. Some defects are hidden by sheets because of the move of carbon sheets, which reduces rate capacity. This paper reveals exposing inner defects of carbon sheets have essential influence on sodium-ion diffusion to achieve high rate performance. Unlabelled Image • The accumulation/exfoliation rate of carbon sheets is acquired by ID/IG value. • Stable rate performance is decided by exposed inner defects near pores. • The etching degree of carbon sheets is achieved by their thickness. [ABSTRACT FROM AUTHOR]

Constructing polycrystalline structure is an effective strategy to improve the electrochemical performance of electrode materials. To enhance the electroactivity of anisotropic VO 2 (M), polycrystalline VO 2 (M) with well-dispersed crystalline zones is successfully synthesized by a facile one-step hydrothermal method, and then their electrochemical performances as an anode of lithium-ion batteries are systematically explored. Results show that the synergistic effect of crystalline zones and amorphous matrices in polycrystalline structure can dramatically activate the anisotropic VO 2 (M) electrode, which contributes to increasing the electroactive zones and facilitating the charge transfer kinetics. Compared with single-crystal VO 2 (M), polycrystalline VO 2 (M) shows the significantly enhanced electrochemical performance, delivering a high reversible capacity of 476 mAhg−1 at 100 mAg−1 after 150 cycles, which is far superior to the theoretical capacity and the reported mixture of VO 2 (M) and VO 2 (B). This work opens up new insights for the activation of anisotropic electrode materials. • Polycrystalline VO 2 (M) with well-dispersed crystalline zones is synthesized. • Synergistic effect of crystalline zones and amorphous matrices is revealed. • The activity of anisotropic VO 2 (M) electrode is dramatically improved. • Polycrystalline VO 2 (M) shows capacity of 476 mAhg−1 at 100 mAg−1 after 150 cycles. [ABSTRACT FROM AUTHOR]

Owing to the high theoretical capacity, Sb 2 Se 3 has been regarded as one of the best choices for Sodium-ion batteries (SIBs) anode materials. However, Sb 2 Se 3 anode suffers from huge volume change with poor electrode structure stability, resulting in limited cycling and rate performance. Herein, inspired by the formation of inclusion complex an effective strategy for improving unstable molecules in biological fields, we encapsulate Sb 2 Se 3 in capsular carbon shell via a hydrothermal and calcinations process. Furthermore, by adjusting the thickness of the capsule carbon shell, an ultra-stable Sb 2 Se 3 electrode structure is realized. Equipped with this ultra-stable electrode structure, Sb 2 Se 3 anode exhibits high capacity of 475 mA h g−1 at 2 A g−1 even after 600 cycles, showing compelling advantage on Na storage performance compared to other reported Sb-based anode materials. The analysis results indicate that the intact capsular carbon shell can effectively remit huge volume change of Sb 2 Se 3 , and act like a reaction vessel in which the sodiation/desodiation reaction of Sb 2 Se 3 is carried out regularly. Therefore, this ultra-stable electrode provides stable redox reactions, easy charge transfer and fast sodium ion diffusion, resulting in excellent Na storage performance of Sb 2 Se 3 anode. Encapsulating Sb 2 Se 3 in capsular carbon shell to from inclusion complex can achieve ultra-stable electrode structure with excellent Na storage performance. Image 1 • An ultra-stable Sb 2 Se 3 anode is realized by encapsulating Sb 2 Se 3 in a capsular carbon shell. • The as-prepared ultra-stable Sb 2 Se 3 anode exhibits high capacity of 475 mA h g−1 at 2 A g−1 after 600 cycles. • Forming inclusion complex is an effective strategy to achieve ultra-stable structure with good Na storage performance. [ABSTRACT FROM AUTHOR]

As an indispensable part of lithium-ion batteries (LIBs), the quality of solid-electrolyte interphase (SEI) influences directly the electrochemical performance. α-FeOOH with superior theoretical capacities, low cost, and environmental friendliness has been regarded as a promising anode of LIBs. In this work, we found that the hydroxyl groups on the surface of α-FeOOH bond with organic electrolytes that forming an inferior SEI layer contained excessive ROCO 2 Li, finally causing a poor Li+ transport. Thus, we construct a novel heterostructure of spindle-like α-FeOOH nanorods embedded in mulberry-like Fe 2 O 3 sphere on reduced graphene oxide sheets (F@F/C) based on the dissolution-recrystallization mechanism to optimize the composition of SEI layers. The content of ROCO 2 Li is decreased as expected in the SEI of F@F/C electrode, which diminish the ionic transfer impedance in the interface and provide more alternative diffusion pathways. As expected, the heterostructural hybrid achieves an excellent electrode performance with a reversible capacity about 1800 mAh g−1 at 0.2 A g−1 after 300 cycles. Even cycled at a high current density of 1 A g−1, the hybrid also remains 1050 mAh g−1 after 600 cycles with a capacity decay rate of only 0.005% per cycle. • A heterostructure of spindle-like α-FeOOH nanorods embed in mulberry-like Fe 2 O 3 sphere is rationally constructed. • Embedded architecture optimizes the proportion of Li 2 CO 3 and ROCO 2 Li in SEI to diminish ionic transfer impedance. • Embedded architecture provides more alternative diffusion pathways to improve ionic diffusion kinetics significantly. [ABSTRACT FROM AUTHOR]