Influenza a Neuraminidase-Based Bivalent mRNA Vaccine Induces Th1-Type Immune Response and Provides Protective Effects in Mice.

Vaccines are one of the most effective means of preventing influenza A, typically containing the hemagglutinin (HA) of the influenza A virus. However, antigenic drift and shift of the influenza A virus can lead to instability in vaccine efficacy. Compared to HA, the antigenic variation rate of neuraminidase (NA) is slower. In traditional inactivated influenza vaccines, although they contain a certain amount of NA, there are significant differences between different batches, which cannot consistently induce NA-based immune responses. Therefore, NA is often overlooked in vaccine development. In this study, we report an mRNA vaccine encoding the NA of two strains of influenza A virus. The experimental results demonstrated that when matched with the viral strain, this mRNA vaccine induced high levels of neutralizing antibodies, providing a protective effect to mice in viral challenge experiments, and this immune response was shown to be biased towards the Th1 type. In summary, this study demonstrates that NA is a promising potential antigen, providing new insights for the development of influenza A virus vaccines.

USP18 Stabilized FTO Protein to Activate Mitophagy in Ischemic Stroke Through Repressing m6A Modification of SIRT6.

Ischemic stroke (IS) is a dangerous cerebrovascular disorder with a significant incidence and death rate. Ubiquitin-specific peptidase 18 (USP18) has been proven to mitigate ischemic brain damage; however, its potential regulatory mechanisms remain unclear. In vivo and in vitro models of IS were established by middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R). Neurocyte injury was detected by MTT, LDH, ROS level, mitochondrial membrane potential (Δψm), and flow cytometry. Molecular expression was evaluated by qPCR, Western blotting, and immunofluorescence staining. Molecular mechanisms were determined by Co-IP, RIP, and MeRIP. IS injury was determined by neurological behavior score and TTC staining. Mitophagy was observed by TEM. USP18 and fat mass and obesity-associated protein (FTO) expression declined after OGD/R. Dysfunctional mitochondrial and apoptosis in OGD/R-stimulated neurocytes were eliminated by USP18/FTO overexpression via mitophagy activation. USP18-mediated de-ubiquitination was responsible for increasing FTO protein stability. Up-regulation of FTO protein restrained m6A modification of sirtuin6 (SIRT6) in a YTHDF2-dependent manner to enhance SIRT6 expression and subsequent activation of AMPK/PGC-1α/AKT signaling. FTO induced mitophagy to ameliorate nerve cell damage through SIRT6/AMPK/PGC-1α/AKT pathway. Finally, USP18/FTO overexpression relieved IS in rats via triggering SIRT6/AMPK/PGC-1α/AKT axis-mediated mitophagy. USP18 increased FTO protein stability to trigger SIRT6-induced mitophagy, thus mitigating IS. Our data unravel the novel neuroprotective mechanism of USP18 and suggest its potential as a promising treatment target for IS.

Association of sex hormones with non-alcoholic fatty liver disease: An observational and Mendelian randomization study.

BACKGROUND AND AIMS: Sex-specific associations of sex hormone-binding globulin (SHBG) and bioavailable testosterone (BAT) with NAFLD remain indeterminate. We aimed to explore observational and genetically determined relationships between each hormone and NAFLD. METHODS: We included 187 395 men and 170 193 women from the UK Biobank. Linear and nonlinear Cox regression models and Mendelian randomization (MR) analysis were used to test the associations. RESULTS: During 12.49 years of follow-up, 2209 male and 1886 female NAFLD cases were documented. Elevated SHBG levels were linearly associated with a lower risk of NAFLD in women (HR (95% CI), .71 (.63, .79)), but not in men (a "U" shape, pnon-linear < .001). Higher BAT levels were associated with a lower NAFLD risk in men (HR (95% CI), .81 (.71, .93)) but a higher risk in women (HR (95% CI): 1.25 (1.15, 1.36)). Genetically determined SHBG and BAT levels were linearly associated with NAFLD risk in women (OR (95% CI): .57 (.38, .87) and 2.21 (1.41, 3.26) respectively); in men, an "L-shaped" MR association between SHBG levels and NAFLD risk was found (pnon-linear = .016). The bidirectional MR analysis further revealed the effect of NAFLD on SHBG and BAT levels in both sexes. CONCLUSIONS: Consistently, linear associations of lower SHBG and higher BAT levels with increased NAFLD risk were both conventionally and genetically found in women, while in men, SHBG acts in a nonlinear manner. In addition, NAFLD may affect SHBG and BAT levels.

BMSC-derived exosomal miR-148b-3p attenuates OGD/R-induced HMC3 cell activation by targeting DLL4 and Notch1.

Bone mesenchymal stem cell (BMSC)-derived exosome (BMSC-Exo) could be a treatment method for ischemic injury. In ischemic cerebrovascular disease (IC), microglia is pivotal in neuronal damage and remodeling. This study explores the mechanisms of BMSC-Exo miR-148b-3p in regulating oxygen-glucose deprivation/reoxygenation (OGD/R)-induced human microglial clone 3 (HMC3) cell activation. Transmission electron microscopy (TEM) and qNano were used to assess BMSC-Exo features. The functions of BMSC-Exo miR-148 b-3p in OGD/R-induced HMC3 cell activation were explored via MTT assay, flow cytometry, scratch, transwell, and enzyme-linked immunosorbent assay (ELISA) assays. A dual-luciferase reporter assay was performed to determine the relationship between miR-148b-3p and Delta-like ligand 4(DDL4) or neurogenic locus notch homolog protein 1 (Notch1). OGD/R decreased miR-148b-3p expression in HMC3 cells. After BMSC-Exo treatment, miR-148b-3p expression was upregulated, cell viability and migration were inhibited, cell cycles remained in the G0/G1 phase, and proinflammatory cytokines were decreased in OGD/R-induced HMC3 cells. More importantly, BMSC-Exo miR-148b-3p could further strengthen BMSC-Exo effects. DDL4 and Notch1 are direct targets of miR-148b-3p, respectively. Moreover, the knockdown of DLL4 or Notch1 could inhibit OGD/R-induced HMC3 cell activation. BMSC-Exo miR-148b-3p inhibited OGD/R-induced HMC3 cell activation via inhibiting DLL4 and Notch1 expression, which provided a new strategy for treating cerebral ischemia.

Cold Temperature Direct Air CO2 Capture with Amine-Loaded Metal-Organic Framework Monoliths.

Zeolites, silica-supported amines, and metal-organic frameworks (MOFs) have been demonstrated as promising adsorbents for direct air CO2 capture (DAC), but the shaping and structuring of these materials into sorbent modules for practical processes have been inadequately investigated compared to the extensive research on powder materials. Furthermore, there have been relatively few studies reporting the DAC performance of sorbent contactors under cold, subambient conditions (temperatures below 20 °C). In this work, we demonstrate the successful fabrication of adsorbent monoliths composed of cellulose acetate (CA) and adsorbent particles such as zeolite 13X and MOF MIL-101(Cr) by a 3D printing technique: solution-based additive manufacturing (SBAM). These monoliths feature interpenetrated macroporous polymeric frameworks in which microcrystals of zeolite 13X or MIL-101(Cr) are evenly distributed, highlighting the versatility of SBAM in fabricating monoliths containing sorbents with different particle sizes and density. Branched poly(ethylenimine) (PEI) is successfully loaded into the CA/MIL-101(Cr) monoliths to impart CO2 uptakes of 1.05 mmol gmonolith-1 at -20 °C and 400 ppm of CO2. Kinetic analysis shows that the CO2 sorption kinetics of PEI-loaded MIL-101(Cr) sorbents are not compromised in the monoliths compared to the powder sorbents. Importantly, these monoliths exhibit promising working capacities (0.95 mmol gmonolith-1) over 14 temperature swing cycles with a moderate regeneration temperature of 60 °C. Dynamic breakthrough experiments at 25 °C under dry conditions reveal a CO2 uptake capacity of 0.60 mmol gmonolith-1, which further increases to 1.05 and 1.43 mmol gmonolith-1 at -20 °C under dry and humid (70% relative humidity) conditions, respectively. Our work showcases the successful implementation of SBAM in making DAC sorbent monoliths with notable CO2 capture performance over a wide range of sorption temperatures, suggesting that SBAM can enable the preparation of efficient sorbent contactors in various form factors for other important chemical separations.

Direct Air Capture of CO2 Using Amine/Alumina Sorbents at Cold Temperature.

Rising CO2 emissions are responsible for increasing global temperatures causing climate change. Significant efforts are underway to develop amine-based sorbents to directly capture CO2 from air (called direct air capture (DAC)) to combat the effects of climate change. However, the sorbents' performances have usually been evaluated at ambient temperatures (25 °C) or higher, most often under dry conditions. A significant portion of the natural environment where DAC plants can be deployed experiences temperatures below 25 °C, and ambient air always contains some humidity. In this study, we assess the CO2 adsorption behavior of amine (poly(ethyleneimine) (PEI) and tetraethylenepentamine (TEPA)) impregnated into porous alumina at ambient (25 °C) and cold temperatures (-20 °C) under dry and humid conditions. CO2 adsorption capacities at 25 °C and 400 ppm CO2 are highest for 40 wt% TEPA-incorporated γ-Al2O3 samples (1.8 mmol CO2/g sorbent), while 40 wt % PEI-impregnated γ-Al2O3 samples exhibit moderate uptakes (0.9 mmol g-1). CO2 capacities for both PEI- and TEPA-incorporated γ-Al2O3 samples decrease with decreasing amine content and temperatures. The 40 and 20 wt % TEPA sorbents show the best performance at -20 °C under dry conditions (1.6 and 1.1 mmol g-1, respectively). Both the TEPA samples also exhibit stable and high working capacities (0.9 and 1.2 mmol g-1) across 10 cycles of adsorption-desorption (adsorption at -20 °C and desorption conducted at 60 °C). Introducing moisture (70% RH at -20 and 25 °C) improves the CO2 capacity of the amine-impregnated sorbents at both temperatures. The 40 wt% PEI, 40 wt % TEPA, and 20 wt% TEPA samples show good CO2 uptakes at both temperatures. The results presented here indicate that γ-Al2O3 impregnated with PEI and TEPA are potential materials for DAC at ambient and cold conditions, with further opportunities to optimize these materials for the scalable deployment of DAC plants at different environmental conditions.

Associations of vitamin D-related single nucleotide polymorphisms with post-stroke depression among ischemic stroke population.

Objective: To investigate the relationship between single nucleotide polymorphisms (SNPs) related to vitamin D (VitD) metabolism and post-stroke depression (PSD) in patients with ischemic stroke. Methods: A total of 210 patients with ischemic stroke were enrolled at the Department of Neurology in Xiangya Hospital, Central South University, from July 2019 to August 2021. SNPs in the VitD metabolic pathway (VDR, CYP2R1, CYP24A1, and CYP27B1) were genotyped using the SNPscan™ multiplex SNP typing kit. Demographic and clinical data were collected using a standardized questionnaire. Multiple genetic models including dominant, recessive, and over-dominant models were utilized to analyze the associations between SNPs and PSD. Results: In the dominant, recessive, and over-dominant models, no significant association was observed between the selected SNPs in the CYP24A1 and CYP2R1 genes and PSD. However, univariate and multivariate logistic regression analysis revealed that the CYP27B1 rs10877012 G/G genotype was associated with a decreased risk of PSD (OR: 0.41, 95% CI: 0.18-0.92, p = 0.030 and OR: 0.42, 95% CI: 0.18-0.98, p = 0.040, respectively). Furthermore, haplotype association analysis indicated that rs11568820-rs1544410-rs2228570-rs7975232-rs731236 CCGAA haplotype in the VDR gene was associated with a reduced risk of PSD (OR: 0.14, 95% CI: 0.03-0.65, p = 0.010), whereas no significant association was observed between haplotypes in the CYP2R1 and CYP24A1 genes and PSD. Conclusion: Our findings suggest that the polymorphisms of VitD metabolic pathway genes VDR and CYP27B1 may be associated with PSD in patients with ischemic stroke.

The role of indoleamine 2,3-dioxygenase 1 in early-onset post-stroke depression.

Background: The immune-inflammatory response has been widely considered to be involved in the pathogenesis of post-stroke depression (PSD), but there is ambiguity about the mechanism underlying such association. Methods: According to Diagnostic and Statistical Manual of Mental Disorders (5th edition), depressive symptoms were assessed at 2 weeks after stroke onset. 15 single nucleotide polymorphisms (SNPs) in genes of indoleamine 2,3-dioxygenase (IDO, including IDO1 and IDO2) and its inducers (including pro-inflammatory cytokines interferon [IFN]-γ, tumor necrosis factor [TNF]-α, interleukin [IL]-1ß, IL-2 and IL-6) were genotyped using SNPscan™ technology, and serum IDO1 levels were detected by double-antibody sandwich enzyme-linked immune-sorbent assay. Results: Fifty-nine patients (31.72%) were diagnosed with depression at 2 weeks after stroke onset (early-onset PSD). The IDO1 rs9657182 T/T genotype was independently associated with early-onset PSD (adjusted odds ratio [OR] = 3.008, 95% confidence interval [CI] 1.157-7.822, p = 0.024) and the frequency of rs9657182 T allele was significantly higher in patients with PSD than that in patients with non-PSD (χ2 = 4.355, p = 0.037), but these results did not reach the Bonferroni significance threshold (p > 0.003). Serum IDO1 levels were also independently linked to early-onset PSD (adjusted OR = 1.071, 95% CI 1.002-1.145, p = 0.044) and patients with PSD had higher serum IDO1 levels than patients with non-PSD in the presence of the rs9657182 T allele but not homozygous C allele (t = -2.046, p = 0.043). Stroke patients with the TNF-α rs361525 G/G genotype had higher serum IDO1 levels compared to those with the G/A genotype (Z = -2.451, p = 0.014). Conclusions: Our findings provided evidence that IDO1 gene polymorphisms and protein levels were involved in the development of early-onset PSD and TNF-α polymorphism was associated with IDO1 levels, supporting that IDO1 which underlie strongly regulation by cytokines may be a specific pathway for the involvement of immune-inflammatory mechanism in the pathophysiology of PSD.

Support Pore Structure and Composition Strongly Influence the Direct Air Capture of CO2 on Supported Amines.

A variety of amine-impregnated porous solid sorbents for direct air capture (DAC) of CO2 have been developed, yet the effect of amine-solid support interactions on the CO2 adsorption behavior is still poorly understood. When tetraethylenepentamine (TEPA) is impregnated on two different supports, commercial γ-Al2O3 and MIL-101(Cr), they show different trends in CO2 sorption when the temperature (-20 to 25 °C) and humidity (0-70% RH) of the simulated air stream are varied. In situ IR spectroscopy is used to probe the mechanism of CO2 sorption on the two supported amine materials, with weak chemisorption (formation of carbamic acid) being the dominant pathway over MIL-101(Cr)-supported TEPA and strong chemisorption (formation of carbamate) occurring over γ-Al2O3-supported TEPA. Formation of both carbamic acid and carbamate species is enhanced over the supported TEPA materials under humid conditions, with the most significant enhancement observed at -20 °C. However, while equilibrium H2O sorption is high at cold temperatures (e.g., -20 °C), the effect of humidity on a practical cyclic DAC process is expected to be minimal due to slow H2O uptake kinetics. This work suggests that the CO2 capture mechanisms of impregnated amines can be controlled by adjusting the degree of amine-solid support interaction and that H2O adsorption behavior is strongly affected by the properties of the support materials. Thus, proper selection of solid support materials for amine impregnation will be important for achieving optimized DAC performance under varied deployment conditions, such as cold (e.g., -20 °C) or ambient temperature (e.g., 25 °C) operations.

Injectable decellularized dental pulp matrix-functionalized hydrogel microspheres for endodontic regeneration.

The sufficient imitation of tissue structures and components represents an effective and promising approach for tissue engineering and regenerative medicine applications. Dental pulp disease is one of the most common oral diseases, although functional pulp regeneration remains challenging. Herein, we propose a strategy that employs hydrogel microspheres incorporated with decellularized dental pulp matrix-derived bioactive factors to simulate a pulp-specific three-dimensional (3D) microenvironment. The dental pulp microenvironment-specific microspheres constructed by this regenerative strategy exhibited favorable plasticity, biocompatibility, and biological performances. Human dental pulp stem cells (hDPSCs) cultured on the constructed microspheres exhibited enhanced pulp-formation ability in vitro. Furthermore, the hDPSCs-microcarriers achieved the regeneration of pulp-like tissue and new dentin in a semi-orthotopic model in vivo. Mechanistically, the decellularized pulp matrix-derived bioactive factors mediated the multi-directional differentiation of hDPSCs to regenerate the pulp tissue by eliciting the secretion of crucial bioactive cues. Our findings demonstrated that a 3D dental pulp-specific microenvironment facilitated by hydrogel microspheres and dental pulp-specific bioactive factors regenerated the pulp-dentin complex and could be served as a promising treatment option for dental pulp disease. STATEMENT OF SIGNIFICANCE: Injectable bioscaffolds are increasingly used for regenerative endodontic treatment. Despite their success related to their ability to load stem cells, bioactive factors, and injectability, conventional bulk bioscaffolds have drawbacks such as ischemic necrosis in the central region. Various studies have shown that ischemic necrosis in the central region can be corrected by injectable hydrogel microspheres. Unfortunately, pristine microspheres or microspheres without dental pulp-specific bioactive factor would oftentimes fail to regulate stem cells fates in dental pulp multi-directional differentiation. Our present study reported the biofabrication of dental pulp-derived decellularized matrix functionalized gelatin microspheres, which contained dental pulp-specific bioactive factors and have the potential application in endodontic regeneration.

Association of homocysteine and polymorphism of methylenetetrahydrofolate reductase with early-onset post stroke depression.

Background: Homocysteine (Hcy) has been indicated to be involved in pathophysiology of post stroke depression (PSD). There is a lack of research to study the relationship between Hcy metabolism genes and PSD. Our study aims to investigate the relationship among Hcy metabolism genes, Hcy, and early-onset PSD. Materials and methods: We recruited 212 patients with stroke and collected their peripheral blood sample, clinical data, and laboratory test on admission. 12 single nucleotide polymorphisms (SNPs) in methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), and methionine synthase (MTR) genes were genotyped by high-resolution melt analysis. PSD was diagnosed by DSM-V at 2 weeks after stroke. Binary logistic regression and haplotype analysis were used to examine the association between Hcy metabolism genes and PSD. Mediation analysis was performed to clarify whether the SNPs exerted their effect on PSD by affecting the Hcy level. Results: 81 patients were diagnosed with PSD, and the incidence rate was 38.2%. Hcy level in PSD group was significantly higher than it in non-PSD group (p = 0.019). MTHFR rs1801133 AA genotype an A allele were associated with an elevated risk of PSD after adjustment for some confounding factors (OR = 4.021, 95% CI: 1.459∼11.080, p = 0.007 for AA genotype; OR = 1.808, 95% CI: 1.172∼2.788, p = 0.007 for A allele). Furthermore, the effect of MTHFR rs1801133 AA genotype on PSD was mediated by Hcy (OR = 1.569, 95% CI: 0.013∼3.350, p < 0.05). Conclusion: MTHFR rs1801133 and Hcy were associated with PSD, and MTHFR rs1801133 may exert an effect on PSD via mediating Hcy level. This offers a new perspective for treating PSD and understanding the mechanism of PSD.

Humans combine value learning and hypothesis testing strategically in multi-dimensional probabilistic reward learning.

Realistic and complex decision tasks often allow for many possible solutions. How do we find the correct one? Introspection suggests a process of trying out solutions one after the other until success. However, such methodical serial testing may be too slow, especially in environments with noisy feedback. Alternatively, the underlying learning process may involve implicit reinforcement learning that learns about many possibilities in parallel. Here we designed a multi-dimensional probabilistic active-learning task tailored to study how people learn to solve such complex problems. Participants configured three-dimensional stimuli by selecting features for each dimension and received probabilistic reward feedback. We manipulated task complexity by changing how many feature dimensions were relevant to maximizing reward, as well as whether this information was provided to the participants. To investigate how participants learn the task, we examined models of serial hypothesis testing, feature-based reinforcement learning, and combinations of the two strategies. Model comparison revealed evidence for hypothesis testing that relies on reinforcement-learning when selecting what hypothesis to test. The extent to which participants engaged in hypothesis testing depended on the instructed task complexity: people tended to serially test hypotheses when instructed that there were fewer relevant dimensions, and relied more on gradual and parallel learning of feature values when the task was more complex. This demonstrates a strategic use of task information to balance the costs and benefits of the two methods of learning.

Iron corroded granules inhibiting vascular smooth muscle cell proliferation.

In-stent restenosis after interventional therapy remains a severe clinical complication. Current evidence indicates that neointimal hyperplasia induced by vascular smooth muscle cell (VSMC) proliferation is a major cause of restenosis. Thus, inhibiting VSMC proliferation is critical for preventing in-stent restenosis. The incidence of restenosis was reduced in nitrided iron-based stents (hereafter referred to as iron stents). We hypothesized that the corroded granules produced by the iron stent would prevent in-stent restenosis by inhibiting VSMC proliferation. To verify this hypothesis, we introduced a dynamic circulation device to analyze the components of corroded granules. To investigate the effects of corroded granules on VSMC proliferation, we implanted the corroded iron stent into the artery of the atherosclerotic artery stenosis model. Moreover, we explored the mechanism underlying the inhibition of VSMC proliferation by iron corroded granules. The results indicated that iron stent produced the corroded granules after implantation, and the main component of the corrosion granules was iron oxide. Remarkably, the corroded granules reduced the neointimal hyperplasia in an atherosclerotic artery stenosis model, and iron corroded granules decreased the neointimal hyperplasia by inhibiting VSMC proliferation. In addition, we revealed that corroded granules reduced VSMC proliferation by activating autophagy through the AMPK/mTOR signaling pathway. Importantly, safety of iron corroded granules was evaluated and proved to be satisfactory hemocompatibility in rabbit model. Overall, the role of corroded granules in restenosis prevention was described for the first time. This finding highlighted the implication of corroded granules produced by iron stent in inhibiting VSMC proliferation, pointing to a new direction to prevent in-stent restenosis.

Improvement of Distance Measurement Based on Dispersive Interferometry Using Femtosecond Optical Frequency Comb.

Since the dispersive interferometry (DPI) based on optical frequency combs (OFCs) was proposed, it has been widely used in absolute distance measurements with long-distance and high precision. However, it has a serious problem for the traditional DPI based on the mode-locked OFC. The error of measurements caused by using the fast Fourier transform (FFT) algorithm to process signals cannot be overcome, which is due to the non-uniform sampling intervals in the frequency domain of spectrometers. Therefore, in this paper, we propose a new mathematical model with a simple form of OFC to simulate and analyze various properties of the OFC and the principle of DPI. Moreover, we carry out an experimental verification, in which we adopt the Lomb-Scargle algorithm to improve the accuracy of measurements of DPI. The results show that the Lomb-Scargle algorithm can effectively reduce the error caused by the resolution, and the error of absolute distance measurement is less than 12 µm in the distance of 70 m based on the mode-locked OFC.

Solid-state molecular oxygen activation using ball milling and a piezoelectric material for aerobic oxidation of thiols.

The agitation of BaTiO3 via ball milling converts mechanical energy into electrical energy, leading to the reduction of molecular oxygen via a single electron transfer pathway analogous to the photocatalytic reaction. This mechanoredox strategy for the oxidative coupling of thiols could eliminate waste and develop a recyclable methodology to accomplish organic transformations in a greener fashion, exhibiting promising potential for large-scale chemical manufacturing.

Energy restriction induced SIRT6 inhibits microglia activation and promotes angiogenesis in cerebral ischemia via transcriptional inhibition of TXNIP.

Energy restriction (ER) protects against cerebral ischemic injury, but the underlying mechanism remains largely unclear. Here, rats were fed ad libitum (AL) or on an alternate-day food deprivation intermittent fasting (IF) diet for 3 months, followed by middle cerebral artery occlusion (MCAO) surgery. The body weight, infarct volume, and neurological deficit score were accessed at the designated time points. ELISA, qRT-PCR, and Western blotting were used to determine cytokine secretion and the expression of SIRT6, TXNIP, and signaling molecules, respectively. Immunofluorescence evaluated microglial activation and angiogenesis in vivo. For in vitro study, oxygen-glucose deprivation/reoxygenation (OGD/R)-treated cell model was generated. MTT and tube formation assays were employed to determine cell viability and tube formation capability. ChIP assay detected chromatin occupancy of SIRT6 and SIRT6-mediated H3 deacetylation. We found that IF or ER mimetics ameliorated cerebral ischemic brain damage and microglial activation, and potentiated angiogenesis in vivo. ER mimetics or SIRT6 overexpression alleviated cerebral ischemia and reperfusion (I/R)-induced injury in vitro. SIRT6 suppressed TXNIP via deacetylation of H3K9ac and H3K56ac in HAPI cells and BMVECs. Downregulation of SIRT6 reversed ER mimetics-mediated protection during cerebral I/R in vitro. Our study demonstrated that ER-mediated upregulation of SIRT6 inhibited microglia activation and potentiated angiogenesis in cerebral ischemia via suppressing TXNIP.

Sub-Ambient Temperature Direct Air Capture of CO2 using Amine-Impregnated MIL-101(Cr) Enables Ambient Temperature CO2 Recovery.

Due to the dramatically increased atmospheric CO2 concentration and consequential climate change, significant effort has been made to develop sorbents to directly capture CO2 from ambient air (direct air capture, DAC) to achieve negative CO2 emissions in the immediate future. However, most developed sorbents have been studied under a limited array of temperature (>20 °C) and humidity conditions. In particular, the dearth of experimental data on DAC at sub-ambient conditions (e.g., -30 to 20 °C) and under humid conditions will severely hinder the large-scale implementation of DAC because the world has annual average temperatures ranging from -30 to 30 °C depending on the location and essentially no place has a zero absolute humidity. To this end, we suggest that understanding CO2 adsorption from ambient air at sub-ambient temperatures, below 20 °C, is crucial because colder temperatures represent important practical operating conditions and because such temperatures may provide conditions where new sorbent materials or enhanced process performance might be achieved. Here we demonstrate that MIL-101(Cr) materials impregnated with amines (TEPA, tetraethylenepentamine, or PEI, poly(ethylenimine)) offer promising adsorption and desorption behavior under DAC conditions in both the presence and absence of humidity under a wide range of temperatures (-20 to 25 °C). Depending on the amine loading and adsorption temperature, the sorbents show different CO2 capture behavior. With 30 and 50 wt % amine loadings, the sorbents show weak and strong chemisorption-dominant CO2 capture behavior, respectively. Interestingly, at -20 °C, the CO2 adsorption capacity of 30 wt % TEPA-impregnated MIL-101(Cr) significantly increased up to 1.12 mmol/g from 0.39 mmol/g at ambient conditions (25 °C) due to the enhanced weak chemisorption. More importantly, the sorbents also show promising working capacities (0.72 mmol/g) over 15 small temperature swing cycles with an ultralow regeneration temperature (-20 °C sorption to 25 °C desorption). The sub-ambient DAC performance of the sorbents is further enhanced under humid conditions, showing promising and stable CO2 working capacities over multiple humid small temperature swing cycles. These results demonstrate that appropriately designed DAC sorbents can operate in a weak chemisorption modality at low temperatures even in the presence of humidity. Significant energy savings may be realized via the utilization of small temperature swings enabled by this weak chemisorption behavior. This work suggests that significant work on DAC materials that operate at low, sub-ambient temperatures is warranted for possible deployment in temperate and polar climates.

Minimal cross-trial generalization in learning the representation of an odor-guided choice task.

There is no single way to represent a task. Indeed, despite experiencing the same task events and contingencies, different subjects may form distinct task representations. As experimenters, we often assume that subjects represent the task as we envision it. However, such a representation cannot be taken for granted, especially in animal experiments where we cannot deliver explicit instruction regarding the structure of the task. Here, we tested how rats represent an odor-guided choice task in which two odor cues indicated which of two responses would lead to reward, whereas a third odor indicated free choice among the two responses. A parsimonious task representation would allow animals to learn from the forced trials what is the better option to choose in the free-choice trials. However, animals may not necessarily generalize across odors in this way. We fit reinforcement-learning models that use different task representations to trial-by-trial choice behavior of individual rats performing this task, and quantified the degree to which each animal used the more parsimonious representation, generalizing across trial types. Model comparison revealed that most rats did not acquire this representation despite extensive experience. Our results demonstrate the importance of formally testing possible task representations that can afford the observed behavior, rather than assuming that animals' task representations abide by the generative task structure that governs the experimental design.

Symptomatic plaque enhancement is associated with early-onset post-stroke depression.

BACKGROUND: The association between imaging features closely associated with symptomatic intracranial atherosclerotic plaques and early-onset post-stroke depression (PSD) is currently unclear. MATERIALS AND METHODS: 76 ischemic stroke patients who underwent high-resolution vessel wall magnetic resonance imaging (HR-VWI) were divided into PSD and non-PSD groups according to their DSM-V diagnoses and HAMD-17 scores at 14 days after onset. Clinical data and the imaging features associated with symptomatic plaques (including the enhancement index (EI), remodeling index, and plaque surface irregularity) were compared between groups. Multifactorial logistic regression analysis was used to find independent predictors of early-onset PSD. Spearman rank correlation analysis explores the association between clinical data, symptomatic plaque imaging features, and HAMD-17 in patients. RESULTS: The sample comprised 36 patients with early-onset PSD. The symptomatic plaque EI and infarct volume were significantly higher in depressed patients than in patients without depression (P < 0.05). Multivariate logistic regression showed that symptomatic plaque EI could be used as an independent predictor of early-onset PSD after correcting for the confounding factor of infarct volume (OR = 1.034, 95% CI:1.014-1.055, P = 0.001). In the total sample, symptomatic plaque EI, infarct volume, and HAMD-17 had a significant positive correlation with each other (P < 0.05). LIMITATIONS: This study focused only on the patients' symptomatic plaques and did not monitor patients' systemic inflammation levels at the time of HR-VWI. CONCLUSIONS: The degree of symptomatic plaque enhancement is an independent predictive imaging marker of early-onset PSD and can be used the early diagnosis of early-onset PSD.

Severity Evaluation of Regional Cerebrovascular Reactivity in Acute Stroke Patients Using SPECT.

BACKGROUND: Cerebrovascular Reactivity (CVR), as measured using perfusion Single Photon Emission Computed Tomography (SPECT), is an important indicator for the treatment and prognosis of cerebrovascular disease, but there are a few studies on acute stroke or small vascular disease using SPECT. OBJECTIVE: This study evaluated the regional severity with quantitatively determined CVR in patients with acute stroke. METHODS: Fifty-eight patients who took brain SPECT images were selected to localize quantitative CVR values. The severity of the disease (Grade 1 to 4) was determined through image-based clinical assessment in the absence and presence of a CVR map, and their results were compared. RESULTS: In 1st diagnosis without the map, the mean CVR values of Grades 2 and 3 were -6.07 % and -9.12 %, respectively (P=0.034), while they were -4.78 % and -12.34 % in 2nd diagnosis with the map, respectively (P<0.001), suggesting that the CVR difference with the map was much more pronounced than without the map. Furthermore, in the ROC analysis, the diagnostic sensitivity between Grades 2 and 3 in the 2nd diagnosis (AUC=0.899, P<0.001) was substantially greater than the 1st diagnosis (AUC=0.646, P=0.048). CONCLUSION: This study demonstrated that the quantitative CVR maps could reinforce the clinical evaluation of cerebral severity by showing that they can provide statistically significant results between severity and CVR. Furthermore, this study was the first to evaluate the effectiveness of quantitative CVR by examining the difference in the presence or absence of CVR in patients with acute stroke.