Unravelling the Photoelectrochemical Water Splitting of Nanometer-Thick Carbon Nitride Layer.

Matching the thickness of the graphitic carbon nitride (CN) nanolayer with the charge diffusion length is expected to compensate for the poor intrinsic conductivity and charge recombination in CN for photoelectrochemical cells (PEC). Herein, the compact CN nanolayer with tunable thickness is in situ coated on carbon fibers. The compact packing along with good contact with the substrate improves the electron transport and alleviates the charge recombination. The PEC investigation shows CN nanolayer of 93 nm-thick yields an optimum photocurrent of 116 µA cm-2 at 1.23 V versus RHE, comparable to most micrometer-thick CN layers, with a low onset potential of 0.2 V in 1 m KOH under 1 sun illumination. This optimum performance suggests the electron diffusion length matches with the thickness of the CN nanolayer. Further deposition of NiFe-layered double hydroxide enhanced the surface water oxidation kinetics, delivering an improved photocurrent of 210 µA cm-2 with IPCE of 12.8% at 400 nm. The CN nanolayer also shows extended potential in PEC organic synthesis. This work experimentally reveals the PEC behavior of the nanometer-thick CN layer, providing new insights into CN in the application of energy and environment-related fields.

Hyperbaric oxygen therapy ameliorates intestinal and systematic inflammation by modulating dysbiosis of the gut microbiota in Crohn's disease.

BACKGROUND: Dysbiosis of the gut microbiota is pivotal in Crohn's disease (CD) and modulated by host physiological conditions. Hyperbaric oxygen therapy (HBOT) is a promising treatment for CD that can regulate gut microbiota. The relationship between HBOT and the gut microbiota in CD remains unknown. METHODS: CD patients were divided into an HBOT group (n = 10) and a control group (n = 10) in this open-label prospective interventional study. The fecal samples before and after HBOT were used for 16 S rRNA gene sequencing and fecal microbiota transplantation (FMT). A colitis mouse model was constructed using dextran sulfate sodium, and intestinal and systematic inflammation was evaluated. The safety and long-term effect of HBOT were observed. RESULTS: HBOT significantly reduced the level of C-reactive protein (CRP) (80.79 ± 42.05 mg/L vs. 33.32 ± 18.31 mg/L, P = 0.004) and the Crohn's Disease Activity Index (CDAI) (274.87 ± 65.54 vs. 221.54 ± 41.89, P = 0.044). HBOT elevated the declined microbial diversity and ameliorated the altered composition of gut microbiota in patients with CD. The relative abundance of Escherichia decreased, and that of Bifidobacterium and Clostridium XIVa increased after HBOT. Mice receiving FMT from donors after HBOT had significantly less intestinal inflammation and serum CRP than the group before HBOT. HBOT was safe and well-tolerated by patients with CD. Combined with ustekinumab, more patients treated with HBOT achieved clinical response (30%vs.70%, P = 0.089) and remission (20%vs.50%, P = 0.160) at week 4. CONCLUSIONS: HBOT modulates the dysbiosis of gut microbiota in CD and ameliorates intestinal and systematic inflammation. HBOT is a safe option for CD and exhibits a promising auxiliary effect to ustekinumab. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200061193. Registered 15 June 2022, https://www.chictr.org.cn/showproj.html?proj=171605 .

ICOS coreceptor signaling inactivates the transcription factor FOXO1 to promote Tfh cell differentiation.

T follicular helper (Tfh) cells are essential in the induction of high-affinity, class-switched antibodies. The differentiation of Tfh cells is a multi-step process that depends upon the co-receptor ICOS and the activation of phosphoinositide-3 kinase leading to the expression of key Tfh cell genes. We report that ICOS signaling inactivates the transcription factor FOXO1, and a Foxo1 genetic deletion allowed for generation of Tfh cells with reduced dependence on ICOS ligand. Conversely, enforced nuclear localization of FOXO1 inhibited Tfh cell development even though ICOS was overexpressed. FOXO1 regulated Tfh cell differentiation through a broad program of gene expression exemplified by its negative regulation of Bcl6. Final differentiation to germinal center Tfh cells (GC-Tfh) was instead FOXO1 dependent as the Foxo1(-/-) GC-Tfh cell population was substantially reduced. We propose that ICOS signaling transiently inactivates FOXO1 to initiate a Tfh cell contingency that is completed in a FOXO1-dependent manner.

A Bcl6 Intronic Element Regulates T Follicular Helper Cell Differentiation.

In response to an intracellular infectious agent, the immune system produces a specific cellular response as well as a T cell-dependent Ab response. Precursor T cells differentiate into effector T cells, including Th1 cells, and T follicular helper (TFH) cells. The latter cooperate with B cells to form germinal centers and induce the formation of Ab-forming plasmacytes. One major focal point for control of T cell differentiation is the transcription factor BCL6. In this study, we demonstrated that the Bcl6 gene is regulated by FOXO1-binding, cis-acting sequences located in a highly conserved region of the first Bcl6 intron. In both mouse and human T cells, deletion of the tandem FOXO1 binding sites increased the expression of BCL6 and enhanced the proportion of TFH cells. These results reveal a fundamental control point for cellular versus humoral immunity.

Clinical, Biomarker, and Research Tests Among US Government Personnel and Their Family Members Involved in Anomalous Health Incidents.

Importance: Since 2015, US government and related personnel have reported dizziness, pain, visual problems, and cognitive dysfunction after experiencing intrusive sounds and head pressure. The US government has labeled these anomalous health incidents (AHIs). Objective: To assess whether participants with AHIs differ significantly from US government control participants with respect to clinical, research, and biomarker assessments. Design, Setting, and Participants: Exploratory study conducted between June 2018 and July 2022 at the National Institutes of Health Clinical Center, involving 86 US government staff and family members with AHIs from Cuba, Austria, China, and other locations as well as 30 US government control participants. Exposures: AHIs. Main Outcomes and Measures: Participants were assessed with extensive clinical, auditory, vestibular, balance, visual, neuropsychological, and blood biomarkers (glial fibrillary acidic protein and neurofilament light) testing. The patients were analyzed based on the risk characteristics of the AHI identifying concerning cases as well as geographic location. Results: Eighty-six participants with AHIs (42 women and 44 men; mean [SD] age, 42.1 [9.1] years) and 30 vocationally matched government control participants (11 women and 19 men; mean [SD] age, 43.8 [10.1] years) were included in the analyses. Participants with AHIs were evaluated a median of 76 days (IQR, 30-537) from the most recent incident. In general, there were no significant differences between participants with AHIs and control participants in most tests of auditory, vestibular, cognitive, or visual function as well as levels of the blood biomarkers. Participants with AHIs had significantly increased fatigue, depression, posttraumatic stress, imbalance, and neurobehavioral symptoms compared with the control participants. There were no differences in these findings based on the risk characteristics of the incident or geographic location of the AHIs. Twenty-four patients (28%) with AHI presented with functional neurological disorders. Conclusions and Relevance: In this exploratory study, there were no significant differences between individuals reporting AHIs and matched control participants with respect to most clinical, research, and biomarker measures, except for objective and self-reported measures of imbalance and symptoms of fatigue, posttraumatic stress, and depression. This study did not replicate the findings of previous studies, although differences in the populations included and the timing of assessments limit direct comparisons.

Neuroimaging Findings in US Government Personnel and Their Family Members Involved in Anomalous Health Incidents.

Importance: US government personnel stationed internationally have reported anomalous health incidents (AHIs), with some individuals experiencing persistent debilitating symptoms. Objective: To assess the potential presence of magnetic resonance imaging (MRI)-detectable brain lesions in participants with AHIs, with respect to a well-matched control group. Design, Setting, and Participants: This exploratory study was conducted at the National Institutes of Health (NIH) Clinical Center and the NIH MRI Research Facility between June 2018 and November 2022. Eighty-one participants with AHIs and 48 age- and sex-matched control participants, 29 of whom had similar employment as the AHI group, were assessed with clinical, volumetric, and functional MRI. A high-quality diffusion MRI scan and a second volumetric scan were also acquired during a different session. The structural MRI acquisition protocol was optimized to achieve high reproducibility. Forty-nine participants with AHIs had at least 1 additional imaging session approximately 6 to 12 months from the first visit. Exposure: AHIs. Main Outcomes and Measures: Group-level quantitative metrics obtained from multiple modalities: (1) volumetric measurement, voxel-wise and region of interest (ROI)-wise; (2) diffusion MRI-derived metrics, voxel-wise and ROI-wise; and (3) ROI-wise within-network resting-state functional connectivity using functional MRI. Exploratory data analyses used both standard, nonparametric tests and bayesian multilevel modeling. Results: Among the 81 participants with AHIs, the mean (SD) age was 42 (9) years and 49% were female; among the 48 control participants, the mean (SD) age was 43 (11) years and 42% were female. Imaging scans were performed as early as 14 days after experiencing AHIs with a median delay period of 80 (IQR, 36-544) days. After adjustment for multiple comparisons, no significant differences between participants with AHIs and control participants were found for any MRI modality. At an unadjusted threshold (P < .05), compared with control participants, participants with AHIs had lower intranetwork connectivity in the salience networks, a larger corpus callosum, and diffusion MRI differences in the corpus callosum, superior longitudinal fasciculus, cingulum, inferior cerebellar peduncle, and amygdala. The structural MRI measurements were highly reproducible (median coefficient of variation <1% across all global volumetric ROIs and <1.5% for all white matter ROIs for diffusion metrics). Even individuals with large differences from control participants exhibited stable longitudinal results (typically, <±1% across visits), suggesting the absence of evolving lesions. The relationships between the imaging and clinical variables were weak (median Spearman ρ = 0.10). The study did not replicate the results of a previously published investigation of AHIs. Conclusions and Relevance: In this exploratory neuroimaging study, there were no significant differences in imaging measures of brain structure or function between individuals reporting AHIs and matched control participants after adjustment for multiple comparisons.

Hydrophobic Carbon Nitride Nanolayer Enables High-Flux Oil/Water Separation with Photocatalytic Antifouling Ability.

Efficient oil/water separation tackles various issues in occasions of oil leakage and oil discharge, such as environmental pollution, recollection of the oil, and saving the water. Herein, a compact superhydrophobic/superoleophilic graphitic carbon nitride nanolayer coated on carbon fiber networks (CNBA/CF) is designed and synthesized for efficient gravity-driven oil/water separation. The CNBA/CF shows excellent oil absorption and an impressive oil/water filtration separation performance. The flux reaches the state-of-art value of 4.29 × 105 L/m2/h for dichloromethane with separation efficiency up to 99%. Successive oil absorption tests, long-term filtration separation, and harsh conditions experiments confirm the remarkable separation and chemical structure stability of the CNBA/CF filter. Besides, the CNBA/CF demonstrates good photocatalytic antifouling ability thanks to the extended visible light absorption and improved charge separation. This work combines the material surface wettability modulation with a photocatalytic self-cleaning property in the fabrication of efficient oil/water separation materials while overcoming the filter fouling issue.

Neuronal tau pathology worsens late-phase white matter degeneration after traumatic brain injury in transgenic mice.

Traumatic brain injury (TBI) causes diffuse axonal injury which can produce chronic white matter pathology and subsequent post-traumatic neurodegeneration with poor patient outcomes. Tau modulates axon cytoskeletal functions and undergoes phosphorylation and mis-localization in neurodegenerative disorders. The effects of tau pathology on neurodegeneration after TBI are unclear. We used mice with neuronal expression of human mutant tau to examine effects of pathological tau on white matter pathology after TBI. Adult male and female hTau.P301S (Tg2541) transgenic and wild-type (Wt) mice received either moderate single TBI (s-TBI) or repetitive mild TBI (r-mTBI; once daily × 5), or sham procedures. Acutely, s-TBI produced more extensive axon damage in the corpus callosum (CC) as compared to r-mTBI. After s-TBI, significant CC thinning was present at 6 weeks and 4 months post-injury in Wt and transgenic mice, with homozygous tau expression producing additional pathology of late demyelination. In contrast, r-mTBI did not produce significant CC thinning except at the chronic time point of 4 months in homozygous mice, which exhibited significant CC atrophy (- 29.7%) with increased microgliosis. Serum neurofilament light quantification detected traumatic axonal injury at 1 day post-TBI in Wt and homozygous mice. At 4 months, high tau and neurofilament in homozygous mice implicated tau in chronic axon pathology. These findings did not have sex differences detected. Conclusions: Neuronal tau pathology differentially exacerbated CC pathology based on injury severity and chronicity. Ongoing CC atrophy from s-TBI became accompanied by late demyelination. Pathological tau significantly worsened CC atrophy during the chronic phase after r-mTBI.

DHRS4-AS1 regulate gastric cancer apoptosis and cell proliferation by destabilizing DHX9 and inhibited the association between DHX9 and ILF3.

Gastric cancer (GC) causes millions of cancer-related deaths due to anti-apoptosis and rapid proliferation. However, the molecular mechanisms underlying GC cell proliferation and anti-apoptosis remain unclear. The expression levels of DHRS4-AS1 in GC were analyzed based on GEO database and recruited GC patients in our institution. We found that DHRS4-AS1 was significantly downregulated in GC. The expression of DHRS4-AS1 in GC tissues showed a significant correlation with tumor size, advanced pathological stage, and vascular invasion. Moreover, DHRS4-AS1 levels in GC tissues were significantly associated with prognosis. DHRS4-AS1 markedly inhibited GC cell proliferation and promotes apoptosis in vitro and in vivo assays. Mechanically, We found that DHRS4-AS1 bound to pro-oncogenic DHX9 (DExH-box helicase 9) and recruit the E3 ligase MDM2 that contributed to DHX9 degradation. We also confirmed that DHRS4-AS1 inhibited DHX9-mediated cell proliferation and promotes apoptosis. Furthermore, we found DHX9 interact with ILF3 (Interleukin enhancer Binding Factor 3) and activate NF-kB Signaling in a ILF3-dependent Manner. Moreover, DHRS4-AS1 can also inhibit the association between DHX9 and ILF3 thereby interfered the activation of the signaling pathway. Our results reveal new insights into mechanisms underlying GC progression and indicate that LncRNA DHRS4-AS1 could be a future therapeutic target and a biomarker for GC diagnosis.

Caprini risk assessment model combined with D-dimer to predict the occurrence of deep vein thrombosis and guide intervention after laparoscopic radical resection of colorectal cancer.

BACKGROUND: To explore the diagnostic value of Caprini risk assessment model (2005) combined with D-dimer for deep vein thrombosis, and to exclude patients with low incidence of thrombosis who might not need anticoagulation after surgery. METHODS: A total of 171 colorectal cancer patients who underwent surgery from January 2022 to August 2022 were enrolled in this study. Caprini risk assessment model was used to evaluate patients the day before surgery, and full-length venous ultrasonography of lower extremity was used to assess whether patients had thrombosis one day before surgery and the sixth day after surgery. The value of D-dimer was measured by enzyme-linked immunosorbent assays on the first day after surgery, and clinical data of patients were collected during hospitalization. RESULTS: A total of 171 patients were divided into IPC Group and IPC + LMWH Group according to whether low molecular weight heparin (LMWH) were used to prevent thrombus after surgery. Eventually, 17.6% (15/85) patients in IPC Group and 7% (6/86) patients in IPC + LMWH Group developed DVT. Through separate analysis of IPC Group, it is found that Caprini score and D-dimer were independent risk factors for DVT (Caprini OR 3.39 [95% CI 1.38-8.32]; P = 0.008, D-Dimer OR 6.142 [95% CI 1.209-31.187]; P = 0.029). The area under ROC curve of Caprini risk assessment model is 0.792 (95% CI 0.69-0.945, P < 0.01), the cut-off value is 9.5, and the area under ROC curve of D-dimer is 0.738 (95%CI 0.555-0.921, P < 0.01), the cut-off value is 0.835 µg/mL, and the area under the ROC curve was 0.865 (95% CI 0.754-0.976, P < 0.01) when both of them were combined. Based on decision curve analysis, it is found that Caprini risk assessment model combined with D-dimer can benefit patients more. All patients are divided into four groups. When Caprini score < 10 and D-dimer < 0.835 µg/mL, only 1.23% (1/81) of patients have thrombosis and LMWH has little significance. When Caprini score > 10 and D-dimer > 0.835 µg/mL, the incidence of DVT is 38.7% (12/31) and LMWH should be considered. CONCLUSIONS: The Caprini risk assessment model and D-dimer can provide more accurate risk stratification for patients after laparoscopic radical resection of colorectal cancer.

Ultrathin and High-Modulus LiBO2 Layer Highly Elevates the Interfacial Dynamics and Stability of Lithium Anode under Wide Temperature Range.

Lithium (Li) metal batteries (LMBs) face huge challenges to achieve long cycling life at wide temperature range owing to the severe dendrite growth at subambient temperature and the intense side reactions with electrolyte at high temperature. Herein, an ultrathin LiBO2 layer with an extremely high Young's modulus of 8.0 GPa is constructed on Li anode via an in situ reaction between Li metal and 4,4,5,5-tetramethyl-1,3,2-dioxa-borolane (TDB) to form LiBO2 @Li anode, which presents two times higher exchange current density than pristine Li anode. The LiBO2 layer presents a strong absorption to Li ions and greatly improves the interfacial dynamics of Li-ion migration, which induces homogenous lithium nucleation and deposition to form a dense lithium layer. Consequently, the Li dendrite growth during cycling at subambient temperature and the side reactions with electrolyte at high temperature are simultaneously suppressed. The LiBO2 @Li/LiNi0.8 Co0.1 Mn0.1 O2 (NCM811) full batteries with limited Li capacity and high cathode mass loading of 9.9 mg cm-2 can steadily cycle for 300 cycles with a capacity retention of 86.6%. The LiBO2 @Li/NCM811 full batteries and LiBO2 @Li/LiBO2 @Li symmetric batteries also present excellent cycling performance at both -20 and 60 °C. This work develops a strategy to achieve outstanding performance of LMBs at wide working temperature-range.

Methodology of the INVestigating traIning assoCiated blasT pAthology (INVICTA) study.

BACKGROUND: Subconcussive blast exposure during military training has been the subject of both anecdotal concerns and reports in the medical literature, but prior studies have often been small and have used inconsistent methods. METHODS: This paper presents the methodology employed in INVestigating traIning assoCiated blasT pAthology (INVICTA) to assess a wide range of aspects of brain function, including immediate and delayed recall, gait and balance, audiologic and oculomotor function, cerebral blood flow, brain electrical activity and neuroimaging and blood biomarkers. RESULTS: A number of the methods employed in INVICTA are relatively easy to reproducibly utilize, and can be completed efficiently, while other measures require greater technical expertise, take longer to complete, or may have logistical challenges. CONCLUSIONS: This presentation of methods used to assess the impact of blast exposure on the brain is intended to facilitate greater uniformity of data collection in this setting, which would enable comparison between different types of blast exposure and environmental circumstances, as well as to facilitate meta-analyses and syntheses across studies.

Downregulation of B3GNT6 is a predictor of poor outcomes in patients with colorectal cancer.

BACKGROUND: The B3GNT6 protein is a member of the O-GlcNAc transferase (OGT) family and is responsible for the production of the core 3 structure of O-glycans. It is generally expressed in the gastrointestinal (GI) tract; however, its clinical significance in colorectal cancer remains largely unexplored. METHODS: We obtained mRNA transcriptomic sequencing data from 3 gene expression omnibus (GEO) datasets (GSE37182, GSE39582, GSE103512) and The Cancer Genome Atlas (TCGA) to compare the B3GNT6 mRNA levels between colorectal cancer and normal tissues and further evaluate its value as a prognostic marker in colorectal cancer. We further validated this at the protein level in our cohort using immunohistochemical staining of B3GNT6 as well as the Human Protein Atlas online database. RESULTS: B3GNT6 expression was downregulated in colorectal cancer tissues as compared to that in the normal tissues at both mRNA and protein levels. Downregulation of B3GNT6 expression was found to be associated with poor overall survival in patients with colorectal cancer as per the data in GSE39582 and TCGA databases. Low B3GNT6 mRNA levels were significantly associated with chromosome instability (CIN) and KRAS mutations in patients with colorectal cancer. Gene set enrichment analysis (GSEA) revealed that low B3GNT6 expression levels in colorectal cancer were associated with increased proteasome activity. CONCLUSIONS: The results of this study demonstrate that low expression of B3GNT6 is a potential biomarker for poor outcomes in patients with CRC. Moreover, the low expression of B3GNT6 may indicate more frequent activation of the KRAS/ERK signaling pathway, high CIN, and increased proteasomal activity. These novel findings may prove helpful for molecular diagnosis and provide a new therapeutic target for colorectal cancer.

Remote blast-related mild traumatic brain injury is associated with differential expression of exosomal microRNAs identified in neurodegenerative and immunological processes.

BACKGROUND: Blast traumatic brain injury (TBI) and subconcussive blast exposure have been associated, pathologically, with chronic traumatic encephalopathy (CTE) and, clinically, with cognitive and affective symptoms, but the underlying pathomechanisms of these associations are not well understood. We hypothesized that exosomal microRNA (miRNA) expression, and their relation to neurobehavioral outcomes among Veterans with blunt or blast mild TBI (mTBI) may provide insight into possible mechanisms for these associations and therapeutic targets. METHODS: This is a subanalysis of a larger Chronic Effects of Neurotrauma Consortium Biomarker Discovery Project. Participants (n = 152) were divided into three groups: Controls (n = 35); Blunt mTBI only (n = 54); and Blast/blast+blunt mTBI (n = 63). Postconcussive and post-traumatic stress symptoms were evaluated using the NSI and PCL-5, respectively. Exosomal levels of 798 miRNA expression were measured. RESULTS: In the blast mTBI group, 23 differentially regulated miRNAs were observed compared to the blunt mTBI group and 23 compared to controls. From the pathway analysis, significantly dysregulated miRNAs in the blast exposure group correlated with inflammatory, neurodegenerative, and androgen receptor pathways. DISCUSSION: Our findings suggest that chronic neurobehavioral symptoms after blast TBI may pathomechanistically relate to dysregulated cellular pathways involved with neurodegeneration, inflammation, and central hormonal regulation.

17α-Ethinyl estradiol-3-sulfate increases survival and hemodynamic functioning in a large animal model of combined traumatic brain injury and hemorrhagic shock: a randomized control trial.

BACKGROUND: Traumatic brain injury (TBI) and severe blood loss resulting in hemorrhagic shock (HS) represent leading causes of trauma-induced mortality, especially when co-occurring in pre-hospital settings where standard therapies are not readily available. The primary objective of this study was to determine if 17α-ethinyl estradiol-3-sulfate (EE-3-SO4) increases survival, promotes more rapid cardiovascular recovery, or confers neuroprotection relative to Placebo following TBI + HS. METHODS: All methods were approved by required regulatory agencies prior to study initiation. In this fully randomized, blinded preclinical study, eighty (50% females) sexually mature (190.64 ± 21.04 days old; 28.18 ± 2.72 kg) Yucatan swine were used. Sixty-eight animals received a closed-head, accelerative TBI followed by removal of approximately 40% of circulating blood volume. Animals were then intravenously administered EE-3-SO4 formulated in the vehicle at 5.0 mg/mL (dosed at 0.2 mL/kg) or Placebo (0.45% sodium chloride solution) via a continuous pump (0.2 mL/kg over 5 min). Twelve swine were included as uninjured Shams to further characterize model pathology and replicate previous findings. All animals were monitored for up to 5 h in the absence of any other life-saving measures (e.g., mechanical ventilation, fluid resuscitation). RESULTS: A comparison of Placebo-treated relative to Sham animals indicated evidence of acidosis, decreased arterial pressure, increased heart rate, diffuse axonal injury and blood-brain barrier breach. The percentage of animals surviving to 295 min post-injury was significantly higher for the EE-3-SO4 (28/31; 90.3%) relative to Placebo (24/33; 72.7%) cohort. EE-3-SO4 also restored pulse pressure more rapidly post-drug administration, but did not confer any benefits in terms of shock index. Primary blood-based measurements of neuroinflammation and blood brain breach were also null, whereas secondary measurements of diffuse axonal injury suggested a more rapid return to baseline for the EE-3-SO4 group. Survival status was associated with biological sex (female > male), as well as evidence of increased acidosis and neurotrauma independent of EE-3-SO4 or Placebo administration. CONCLUSIONS: EE-3-SO4 is efficacious in promoting survival and more rapidly restoring cardiovascular homeostasis following polytraumatic injuries in pre-hospital environments (rural and military) in the absence of standard therapies. Poly-therapeutic approaches targeting additional mechanisms (increased hemostasis, oxygen-carrying capacity, etc.) should be considered in future studies.

Mangiferin prevents the impairment of mitochondrial dynamics and an increase in oxidative stress caused by excessive fluoride in SH-SY5Y cells.

Previous studies both invivo and in vitro have revealed that high levels of fluoride cause neurotoxicity. Mangiferin has been reported to possess antioxidant, antiapoptotic, and anti-inflammatory properties. The present study was designed to characterize the mechanisms by which mangiferin protects against NaF-induced neurotoxicity. Increased levels of proapoptotic Bax, Caspase-3, Caspase-9, and cleaved-caspase 3, as well as a decreased level of antiapoptotic Bcl-2 induced by fluoride in human neuroblastoma SH-SY5Y cells, these effects were prevented by pretreatment of mangiferin. In addition, mangiferin attenuated the enhancement of p-JNK, reductions of Nrf2 and HO-1, and increased level of the mitochondrial fission proteins Drp1 caused by fluoride. Moreover, oxidative stress, as reflected in the levels of reactive oxygen species, 8-hydroxy-2'-deoxyguanosine, and 4-hydroxynonenal, was elevated by fluoride and these effects were again ameliorated by mangiferin. In conclusion, protection by mangiferin against fluoride-induced neurotoxicity involves normalizing the impaired mitochondrial apoptotic pathway and dynamics and reducing oxidative stress via inactivation of the JNK and activation of the Nrf2/HO-1 pathways.

Stabilizing a Lithium Metal Battery by an In Situ Li2S-modified Interfacial Layer via Amorphous-Sulfide Composite Solid Electrolyte.

A novel strategy has been proposed to produce in situ Li2S at the interfacial layer between lithium anode and the solid electrolyte, by using an amorphous-sulfide-LiTFSI-poly(vinylidene difluoride) (PVDF) composite solid electrolyte (SLCSE). Besides retarding the decomposition of PVDF in CSE, the Li2S-modified interfacial layer (SMIL) also improves the wettability between lithium metal and SLCSE which in turn optimizes the lithium deposition process. Our density functional theory calculation results reveal that the migration energy barrier of Li passing through SMIL is much lower than that of Li passing through LiF-modified interfacial layer (FMIL) formed from the decomposition of PVDF. The as-prepared SLCSE shows a Li ionic transference number of 0.44 and Li ion conductivity of 3.42 × 10-4 S/cm at room temperature, and the Li||SLCSE||LiFePO4 cell exhibits an outstanding rate performance with a capacity of 153, 144, 131, and 101 mAh/g at a current density of 0.05, 0.10, 0.25, and 0.50 mA/cm2, respectively.

Dense-Stacking Porous Conjugated Polymer as Reactive-Type Host for High-Performance Lithium Sulfur Batteries.

Commercialization of the lithium-sulfur battery is hampered by bottlenecks like low sulfur loading, high cathode porosity, uncontrollable Li2 Sx deposition and sluggish kinetics of Li2 S activation. Herein, we developed a densely stacked redox-active hexaazatrinaphthylene (HATN) polymer with a surface area of 302 m2 g-1 and a very high bulk density of ca. 1.60 g cm-3 . Uniquely, HATN polymer has a similar redox potential window to S, which facilitates the binding of Li2 Sx and its transformation chemistry within the bulky polymer host, leading to fast Li2 S/S kinetics. The compact polymer/S electrode presents a high sulfur loading of ca. 15 mgs cm-2 (200-µm thickness) with a low cathode porosity of 41 %. It delivers a high areal capacity of ca. 14 mAh cm-2 and good cycling stability (200 cycles) at electrolyte-sulfur (E/S) ratio of 5 µL mgs -1 . The assembled pouch cell delivers a cell-level high energy density of 303 Wh kg-1 and 392 Wh L-1 .

Stable Interface Chemistry and Multiple Ion Transport of Composite Electrolyte Contribute to Ultra-long Cycling Solid-State LiNi0.8 Co0.1 Mn0.1 O2 /Lithium Metal Batteries.

Severe interfacial side reactions of polymer electrolyte with LiNi0.8 Co0.1 Mn0.1 O2 (NCM811) cathode and Li metal anode restrict the cycling performance of solid-state NCM811/Li batteries. Herein, we propose a chemically stable ceramic-polymer-anchored solvent composite electrolyte with high ionic conductivity of 6.0×10-4  S cm-1 , which enables the solid-state NCM811/Li batteries to cycle 1500 times. The Li1.4 Al0.4 Ti1.6 (PO4 )3 nanowires (LNs) can tightly anchor the essential N, N-dimethylformamide (DMF) in poly(vinylidene fluoride) (PVDF), greatly enhancing its electrochemical stability and suppressing the side reactions. We identify the ceramic-polymer-liquid multiple ion transport mechanism of the LNs-PVDF-DMF composite electrolyte by tracking the 6 Li and 7 Li substitution behavior via solid-state NMR. The stable interface chemistry and efficient ion transport of LNs-PVDF-DMF contribute to superior performances of the solid-state batteries at wide temperature range of -20-60 °C.

EphA2-to-YAP pathway drives gastric cancer growth and therapy resistance.

Yes-associated protein (YAP) is a transcriptional coactivator that promotes cell proliferation, stem cell maintenance and tissue homeostasis. The YAP activity is primarily regulated through an inhibitory phosphorylation by the serine/threonine kinases of Hippo pathway. Here, we show that receptor tyrosine kinase (RTK) erythropoietin-producing hepatocellular receptor A2 (EphA2) interacts with and phosphorylates YAP protein, leading to stabilization, nuclear translocation and activation of YAP in gastric cancer (GC) cells. EphA2 induces chemotherapy-resistance by increasing YAP stability and nuclear YAP protein. Knockdown of YAP blocks EphA2-induced tumor growth in GC xenograft mouse models. Importantly, the coactivation of EphA2 and YAP is manifested in clinical human GC, and is related to GC recurrence. Thus, our results establish a novel EphA2-to-YAP pathway that drives GC growth, progression and therapy-resistance, targeting this pathway would be an efficient way for the treatment of GC, particularly chemotherapy-resistant GC.