Triiodothyronine induces a proinflammatory monocyte/macrophage profile and impedes cardiac regeneration.

Neonatal mouse hearts can regenerate post-injury, unlike adult hearts that form fibrotic scars. The mechanism of thyroid hormone signaling in cardiac regeneration warrants further study. We found that triiodothyronine impairs cardiomyocyte proliferation and heart regeneration in neonatal mice after apical resection. Single-cell RNA-Sequencing on cardiac CD45-positive leukocytes revealed a pro-inflammatory phenotype in monocytes/macrophages after triiodothyronine treatment. Furthermore, we observed that cardiomyocyte proliferation was inhibited by medium from triiodothyronine-treated macrophages, while triiodothyronine itself had no direct effect on the cardiomyocytes in vitro. Our study unveils a novel role of triiodothyronine in mediating the inflammatory response that hinders heart regeneration.

ErbB4 deficiency exacerbates olfactory dysfunction in an early-stage Alzheimer's disease mouse model.

Olfactory dysfunction is increasingly recognized as an early indicator of Alzheimer's disease (AD). Aberrations in GABAergic function and the excitatory/inhibitory (E/I) balance within the olfactory bulb (OB) have been implicated in olfactory impairment during the initial stages of AD. While the neuregulin 1 (NRG1)/ErbB4 signaling pathway is known to regulate GABAergic transmission in the brain and is associated with various neuropsychiatric disorders, its specific role in early AD-related olfactory impairment remains incompletely understood. This study demonstrated that olfactory dysfunction preceded cognitive decline in young adult APP/PS1 mice and was characterized by reduced levels of NRG1 and ErbB4 in the OB. Further investigation revealed that deletion of ErbB4 in parvalbumin interneurons reduced GABAergic transmission and increased hyperexcitability in mitral and tufted cells (M/Ts) in the OB, thereby accelerating olfactory dysfunction in young adult APP/PS1 mice. Additionally, ErbB4 deficiency was associated with increased accumulation of Aß and BACE1-mediated cleavage of APP, along with enhanced CDK5 signaling in the OB. NRG1 infusion into the OB was found to enhance GABAergic transmission in M/Ts and alleviate olfactory dysfunction in young adult APP/PS1 mice. These findings underscore the critical role of NRG1/ErbB4 signaling in regulating GABAergic transmission and E/I balance within the OB, contributing to olfactory impairment in young adult APP/PS1 mice, and provide novel insights for early intervention strategies in AD. This work has shown that ErbB4 deficiency increased the burden of Aß, impaired GABAergic transmission, and disrupted the E/I balance of mitral and tufted cells (M/Ts) in the OB, ultimately resulting in olfactory dysfunction in young adult APP/PS1 mice. NRG1 could enhance GABAergic transmission, rescue E/I imbalance in M/Ts, and alleviate olfactory dysfunction in young adult APP/PS1 mice. OB: olfactory bulb, E/I: excitation/inhibition, Pr: probability of release, PV: parvalbumin interneurons, Aß: ß-amyloid, GABA: gamma-aminobutyric acid.

Alkaline Ionic Liquid Microphase Promotes Deep Reduction of CO2 on Copper.

Electrochemical reduction of CO2 to multicarbon (C2+) products using renewable energy sources is an important route to storing sustainable energy and achieving carbon neutrality. It remains a challenge to achieve high C2+ product faraday efficiency (FE) at ampere-level current densities. Herein, we propose the immobilization of an alkaline ionic liquid on copper for promoting the deep reduction of CO2. By this strategy, a C2+ FE of 81.4% can be achieved under a current density of 0.9 A·cm-2 with a half-cell energy conversion efficiency of 47.4% at -0.76 V vs reversible hydrogen electrode (RHE). Particularly, when the current density is as high as 1.8 A·cm-2, the C2+ FE reaches 71.6% at an applied potential of -1.31 V vs RHE. Mechanistic studies demonstrate that the alkaline ionic liquid plays multiple roles of improving the accumulation of CO2 molecules on the copper surface, promoting the activation of the adsorbed CO2, reducing the energy barrier of CO dimerization, stabilizing intermediates, and facilitating the C2+ product formation.

Single Unit-Cell Layered Bi2 Fe4 O9 Nanosheets: Synthesis, Formation Mechanism, and Anisotropic Thermal Expansion.

As an important multiferroic material, pure and low-dimensional phase-stable bismuth ferrite has wide applications. Herein, one-pot hydrothermal method was used to synthesize bismuth ferrite. Almost pure Bi2 Fe4 O9 , BiFeO3 , and their mixture were successfully obtained by controlling the KOH concentration in the hydrothermal solutions. The as-prepared Bi2 Fe4 O9 products were crystalline with Pbam space group, had nanosheet morphology, and tended to aggregate into nanofloret or random stacking. Each Bi2 Fe4 O9 nanosheet was a single crystal with (001) plane as its exposed surface. Single unit-cell layered Bi2 Fe4 O9 nanosheets had a uniform thickness of 1 nm. The surface energies of various (100), (010), and (001) planes were 3.6-4.0, 5.6-15.1, and 1.7-3.0 J m-2 , respectively, in the Bi2 Fe4 O9 crystal. The formation mechanism and structural model of the as-prepared single unit-cell layered Bi2 Fe4 O9 nanosheets have been given. The growth of Bi2 Fe4 O9 nanosheets was discussed. Thermal analysis showed that the Bi2 Fe4 O9 phase was stable up to 1260 K. The thermal expansion behavior of the Bi2 Fe4 O9 nanosheet was nonlinear. The thermal expansion coefficients of the ultrathin Bi2 Fe4 O9 nanosheets on the a-, b-, c-axes, and on the unit-cell volume V were determined, showing an anisotropic thermal expansion behavior. This study is helpful for the controllable synthesis of ultrathin Bi2 Fe4 O9 nanosheets.

Crystalline Structure and Thermal Stability of an Unknown ZIF-L300 Phase.

In recent years, the synthesis, crystalline structure, and applications of zeolite imidazole frameworks (ZIFs) have attracted extensive attention. Since the ZIF-L phase was synthesized, a new phase was observed during the heating process, but its crystal structure is unknown. The unknown new phase, which was named ZIF-L300 in this study, was confirmed again. In this study, the X-ray powder diffraction technique and Rietveld refinement were used to solve the crystalline structure of the unknown ZIF-L300 phase. The results demonstrate that ZIF-L300 has the same chemical formula (ZnC8N4H10) as in ZIF-8 and belongs to a hexagonal structure with a space group of P61. The lattice parameters have been determined as follows: a = b = 8.708(7) Å, c = 24.195(19) Å, α = ß = 90°, and γ = 120°. The X-ray absorption fine structure (XAFS) technique was also used to extract the local atomic structures. The in situ X-ray diffraction (XRD) technique was used to monitor the structural evolution of the as-prepared ZIF-L in a temperature range from room temperature to 600 °C. The results show that the sample experiences a change process from the initial ZIF-L orthorhombic phase (<210 °C), to the ZIF-L300 hexagonal phase (∼300 °C), then to an amorphous phase (∼390 °C), and finally to a zincite ZnO phase (>420 °C). These sorts of structural information are helpful to the application of ZIF materials and enrich the knowledge of the thermal stability of ZIF materials.

Sex bias in alcohol research: A 20-year comparative study.

We aimed to assess the sex-inclusive and sex-based analysis bias in alcohol research for the past 20 years. Data were abstracted from 2988 original research articles published from 2000 through 2019 in 51 representative journals across 9 biomedical disciplines. An analysis in 5-year intervals revealed that the percentage of studies using participants of both sexes was significantly higher between 2015 and 2019 than between 2000 and 2014. When stratified, clinical studies showed a higher percentage of both-sex studies compared to basic studies using animals. The reasons for the use of single-sex cohorts mainly included insufficient participant numbers and misconceptions surrounding the hormonal variability of females. Implementation of the NIH SABV policy promoted the ratio of NIH-funded papers with sex-based analyses. In conclusion, sex bias in alcohol-related biomedical studies has improved over the past 20 years, particularly after the implementation of the SABV policy. Although clinical studies increasingly included sex-based analysis, basic studies were biased towards the use of males.

Hydrothermal Synthesis and Structures of Unknown Intermediate Phase Zn(HCO3)2·H2O Nanoflakes and Final ZnO Nanorods.

The formation mechanism of nanoparticles is of great significance for the controllable synthesis, structural design, and performance optimization of nanomaterials. In this paper, an economical hydrothermal method was used to synthesize zinc oxide (ZnO) nanorods. X-ray diffraction, X-ray absorption fine structure, and small-angle X-ray scattering techniques were used to probe the structural changes. Scanning electron microscopy and high-resolution transmission electron microscopy were used to observe the morphologies of the products. A self-designed in situ temperature-pressure sample cell was used to control the hydrothermal conditions. The results demonstrate that an unknown intermediate phase, Zn(HCO3)2·H2O, was first formed at 50 °C, having a morphology of nanoflakes with a average thickness of about 35 nm. The intermediate phase Zn(HCO3)2·H2O was determined to have a monoclinic structure with space group P1211 and the following lattice parameters: a = 11.567 Å, b = 3.410 Å, c = 5.358 Å, ß = 96.0011°, and Z = 2. After a hydrothermal temperature of 140 °C, CO2 and H2O were evaporated from the Zn(HCO3)2·H2O intermediate product and the ZnO nanorods with a wurtzite structure were formed. The final ZnO nanorods have an average diameter of about 45 nm and an average length of about 2 µm. The axial direction of the ZnO nanorods is the [001] crystallographic direction. By virtue of understanding the formation mechanism, this work is helpful for the controllable synthesis of ZnO nanoparticles.

Water-stable perovskite-silica nanocomposites for encoded microbeads construction and multiplexed detection.

All-inorganic lead halide perovskite nanocrystals exhibiting bright luminescence have great potential as fluorescence elements for optical encoding. However, their limited stability in water hinders the application in biosensing. In this study, novel optical encoded microbeads based on CsPbX3 (X = Cl, Br) nanocrystals are developed and applied in bead-based suspension arrays for the first time. Through the in-situ crystallization of CsPbX3 nanocrystals within mesoporous silica nano-templates (MSNs), accompanied by mesopores collapse after sintering, CsPbX3@MSNs (X3M) nanocomposites with uniform morphology and stable fluorescence intensity in aqueous solutions for up to 50 days are obtained. By assembling X3M with microspheres to form a host-guest structure, an optical encoding microbead (MX3M) library is established by varying the X3M ratio, halide composition, and the size of host microspheres, which can be easily decoded under multi-channel flow cytometer. As a result, MX3M exhibits outstanding capacity for specific target capture and negligible nonspecific absorption performance in the multiplex nucleic acid detection of respiratory viruses, with a low limit of detection (10 copies/rxn). This result highlights the tremendous potential of MX3M encoded microbeads constructed based on CsPbX3 nanocrystals for multiplexed bioassays.

Ultra-stable and highly-bright CsPbBr3 perovskite/silica nanocomposites for miRNA detection based on digital single-nanoparticle counting.

Single-nanoparticle counting (SNPC) based on fluorescent tag (FT) stands out for its capacity to achieve amplification-free and sensitive detection of biomarkers. The stability and luminescence of FT are important to the sensitivity and reliability of SPNC. In this work, we developed novel perovskite/silica nanocomposites by in-situ nanoconfined growth of CsPbBr3 nanocrystals inside mesoporous structure of silica nanoparticles. PbBr(OH) was formed in an alkaline-assisted reaction triggered by water on the surface of CsPbBr3 nanocrystals. The as-obtained nanocomposites, featuring dual protection from silica matrix and PbBr(OH), exhibited high absolute photoluminescence quantum yield (PLQY) of 86.5% and demonstrated outstanding PL stability confronting with water, heat, ultrasound and UV-irradiation, which is desired by SNPC-based biosensor. Thereafter, these nanocomposites were used to construct an operationally friendly SNPC assay for the amplification-free quantification of cancer-associated miRNA. Quantitative detection of miRNA could be accomplished by directly counting the number of nanocomposites using a flow cytometer in this assay. This strategy did not ask for multiple washing steps and demonstrated specific and sensitive detection of miRNA 21, which exhibited a dynamic range of 1-1000 pM and limit of detection of 79 amol. The employment of highly stable perovskite/silica nanocomposites improved the test reliability and stability of SNPC, revealing the vast potential of perovskites in biosensing.

Improving Proton-Conducting Stability by Regulating Pore Size of MOF Materials through Mixed Grinding.

An effective strategy to improve the proton conductivity of metal-organic frameworks (MOFs) is to regulate the pore size of composite materials. In this work, composite materials of MOF-808@MOG-808-X (X is the mass ratios of MOF-808 to MOG-808) was successfully prepared by grinding and blending. MOF-808@MOG-808-1:2 was optimal for its suitable pore structure, which facilitates the practical construction of hydrogen bonding networks, promotes rapid and stable proton conduction, and enables the proton conductivity, achieving a 1 + 1 > 2 effect. At 353 K and 93% relative humidity (RH), the maximum proton conductivity of MOF-808@MOG-808-1:2 reaches 1.08 × 10-1 S·cm-1. Next, MOF-808@MOG-808-1:2 was blended with chitosan (CS) to obtain composite proton exchange membranes (PEMs), namely, CS@MOF-808@MOG-808-1:2-Y (Y = 5%, 10%, or 15%) with the maximum proton conductivity reaching 1.19 × 10-2 S·cm-1 at 353 K and 93% RH for CS@MOF-808@MOG-808-1:2-10% with additional stability. The conductive mechanisms of the composite materials were revealed by activation energy calculation. This investigation not only proposes a simple grinding-blending method for the development of MOF-doped composite materials for proton conductivity but also provides a producting material basis for future applications of MOFs in proton exchange membrane fuel cells (PEMFCs).

Partially Nitrided Ni Nanoclusters Achieve Energy-Efficient Electrocatalytic CO2 Reduction to CO at Ultralow Overpotential.

Electrocatalytic CO2 reduction reaction (CO2 RR) offers a promising strategy to lower CO2 emission while producing value-added chemicals. A great challenge facing CO2 RR is how to improve energy efficiency by reducing overpotentials. Herein, partially nitrided Ni nanoclusters (NiNx ) immobilized on N-doped carbon nanotubes (NCNT) for CO2 RR are reported, which achieves the lowest onset overpotential of 16 mV for CO2 -to-CO and the highest cathode energy efficiency of 86.9% with CO Faraday efficiency >99.0% to date. Interestingly, NiNx /NCNT affords a CO generation rate of 43.0 mol g-1  h-1 at a low potential of -0.572 V (vs RHE). DFT calculations reveal that the NiNx nanoclusters favor *COOH formation with lower Gibbs free energy than isolated Ni single-atom, hence lowering CO2 RR overpotential. As NiNx /NCNT is applied to a membrane electrode assembly system coupled with oxygen evolution reaction, a cell voltage of only 2.13 V is required to reach 100 mA cm-2 , with total energy efficiency of 62.2%.

Amelioration of olfactory dysfunction in a mouse model of Parkinson's disease via enhancing GABAergic signaling.

BACKGROUND: Olfactory dysfunction is among the earliest non-motor symptoms of Parkinson's disease (PD). As the foremost pathological hallmark, α-synuclein initiates the pathology in the olfactory pathway at the early stage of PD, particularly in the olfactory epithelium (OE) and olfactory bulb (OB). However, the local neural microcircuit mechanisms underlying olfactory dysfunction between OE and OB in early PD remain unknown. RESULTS: We observed that odor detection and discrimination were impaired in 6-month-old SNCA-A53T mice, while their motor ability remained unaffected. It was confirmed that α-synuclein increased and accumulated in OB but not in OE. Notably, the hyperactivity of mitral/tufted cells and the excitation/inhibition imbalance in OB were found in 6-month-old SNCA-A53T mice, which was attributed to the impaired GABAergic transmission and aberrant expression of GABA transporter 1 and vesicular GABA transporter in OB. We further showed that tiagabine, a potent and selective GABA reuptake inhibitor, could reverse the impaired olfactory function and GABAergic signaling in OB of SNCA-A53T mice. CONCLUSIONS: Taken together, our findings demonstrate potential synaptic mechanisms of local neural microcircuit underlying olfactory dysfunction at the early stage of PD. These results highlight the critical role of aberrant GABAergic signaling of OB in early diagnosis and provide a potential therapeutic strategy for early-stage PD.

Mesenchymal Stem Cell Therapy for Acetaminophen-related Liver Injury: A Systematic Review and Meta-analysis of Experimental Studies In Vivo.

OBJECTIVE: The efficacy of mesenchymal stem cell (MSC) therapy in acetaminophen-induced liver injury has been investigated in animal experiments, but individual studies with a small sample size cannot be used to draw a clear conclusion. Therefore, we conducted a systematic review and meta-analysis of preclinical studies to explore the potential of using MSCs in acetaminophen- induced liver injury. METHODS: Eight databases were searched for studies reporting the effects of MSCs on acetaminophen hepatoxicity. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used. SYRCLE's risk of bias tool for animal studies was applied to assess the methodological quality. A meta-analysis was performed by using RevMan 5.4 and STATA/ SE 16.0 software. RESULTS: Eleven studies involving 159 animals were included according to PRISMA statement guidelines. Significant associations were found for MSCs with the levels of alanine transaminase (ALT) (standardized mean difference (SMD) - 2.58, p < 0.0001), aspartate aminotransferase (AST) (SMD - 1.75, p = 0.001), glutathione (GSH) (SMD 3.7, p < 0.0001), superoxide dismutase (SOD) (SMD 1.86, p = 0.022), interleukin 10 (IL-10) (SMD 5.14, p = 0.0002) and tumor necrosis factor-α (TNF-α) (SMD - 4.48, p = 0.011) compared with those in the control group. The subgroup analysis showed that the tissue source of MSCs significantly affected the therapeutic efficacy (p < 0.05). CONCLUSION: Our meta-analysis results demonstrate that MSCs could be a potential treatment for acetaminophen- related liver injury. The protocol for this meta-analysis was prospectively registered in PROSPERO (Number: CRD42020212677).

Matrix stiffness-regulated cellular functions under different dimensionalities.

Various cues from the microenvironment in which cells live can regulate cellular functions. In addition to biochemical cues, increasing evidence has demonstrated that mechanical cues (namely, substrate/matrix stiffness in this review) presented by the cell microenvironment are also critically important in regulating cellular functions. However, most studies on stiffness-regulated cellular functions mainly focus on 2D conditions, which might not be able to recapitulate the 3D microenvironment encountered by the cells in vivo. In contrast to the observations in 2D microenvironments, studies have already shown that cells respond differently to mechanical cues under 3D microenvironments. In this review, the mechanisms of cellular mechanosensing and mechanotransduction are briefly presented, followed by the introduction of the most studied 2D/3D platforms. The effects of substrate/matrix stiffness on cellular functions, including cell migration, spreading, proliferation, phenotype, and differentiation, under different dimensionalities are summarized and discussed. Finally, the persisting questions and future outlook are also proposed.

Epidemiological Realities of Alcoholic Liver Disease: Global Burden, Research Trends, and Therapeutic Promise.

Globally, alcohol consumption contributes to more than 3 million deaths each year. While much of its ramifications is preventable, a coherent public health discourse on how to limit alcohol-related harm has been overdue. By synthesizing information from national and global databases, we show in this analysis that alcohol consumption level and alcohol-attributable burden of diseases, particularly alcoholic liver disease (ALD), are intimately linked to national income distribution, cultural norms, religion, sex, age, and health status. Prevalence and burden of ALD are positively associated with economic standing in most countries, which necessitate active governmental control via cost-effective policies, such as the best buys proposed by the World Health Organization. To date, a number of critical questions remain unanswered over the molecular mechanisms underlying ALD pathophysiology; the insights gained thereof should provide new opportunities for the advancement of novel diagnostic and management strategies. In comparison with other prevailing liver diseases (e.g., viral hepatitis and nonalcoholic fatty liver disease), governmental support to ALD investigation has been sluggish in most Western countries and China, resulting in a dearth of breakthroughs on both the basic and clinical research fronts in the past decades. Emerging foci of clinical trials for ALD therapy include empirical use of probiotics, antioxidants, growth factors, monoclonal antibodies against key inflammatory mediators, and technology-enhanced behavioral interventions. In this article, we seek to provide a comprehensive analysis on the progress and challenges in tackling ALD as a global health problem, with particular emphasis on global disease burden, socioeconomic influences, research trends, government roles, and future therapies.

A photo-switchable and thermal-enhanced fluorescent hydrogel prepared from N-isopropylacrylamide with water-soluble spiropyran derivative.

Herein, a photo-switchable and thermal-enhanced fluorescent hydrogel has been fabricated from N-isopropylacrylamide (NIPAAm) with a mixture of water-soluble acryloyl-α-cyclodextrin/acryloyl-α-cyclodextrin-spiropyran (acryloyl-α-CD/ acryloyl-α-CD-SP) as cross-linkers. The physical properties, photochromic properties, and fluorescent behavior of the hydrogel were characterized. The fluorescence emission of the hydrogel can be reversibly switched 'on/off' by UV/visible light irradiation, and meanwhile the fluorescence intensity can be enhanced by increasing the temperature above the volume phase transition temperature (VPTT) of the hydrogel. The hydrogel also shows spatiotemporal fluorescent behavior, excellent cytocompatibility, and fatigue resistance in photochromic and photo-switchable fluorescent behaviors.

Insulin Restores an Altered Corneal Epithelium Circadian Rhythm in Mice with Streptozotocin-induced Type 1 Diabetes.

The mechanisms of corneal epithelial lesions and delayed wound repair, as well as their association with diabetes mellitus, are critical issues for clinical ophthalmologists. To test whether the diabetic condition alters the circadian rhythm in a mouse cornea and whether insulin can synchronise the corneal clock, we studied the effects of streptozotocin-induced diabetes on the mitosis of epithelial cells, the recruitment of leukocytes to the cornea, and the expression of main core clock genes (Clock, Bmal1, Per2, Cry1, and Rev-erbα) in the corneal epithelium. We also assessed the possible effect of insulin on these modifications. Diabetes downregulated Clock, Bmal1, and Per2 expression, upregulated Cry1 and Rev-erbα expression, reduced corneal epithelial mitosis, and increased leukocyte (neutrophils and γδ T-cells) recruitment to the cornea. Early treatments with insulin partially restored the altered rhythmicity in the diabetic cornea. In conclusion, insulin-dependent diabetes altered the normal rhythmicity of the cornea, and insulin administration had a beneficial effect on restoring normal rhythmicity in the diabetic cornea.

Mast Cells Participate in Corneal Development in Mice.

The development of the cornea, a highly specialized transparent tissue located at the anterior of the eye, is coordinated by a variety of molecules and cells. Here, we report that mast cells (MCs), recently found to be involved in morphogenesis, played a potentially important role in corneal development in mice. We show that two different waves of MC migration occurred during corneal development. In the first wave, MCs migrated to the corneal stroma and became distributed throughout the cornea. This wave occurred by embryonic day 12.5, with MCs disappearing from the cornea at the time of eyelid opening. In the second wave, MCs migrated to the corneal limbus and became distributed around limbal blood vessels. The number of MCs in this region gradually increased after birth and peaked at the time of eyelid opening in mice, remaining stable after postnatal day 21. We also show that integrin α4ß7 and CXCR2 were important for the migration of MC precursors to the corneal limbus and that c-Kit-dependent MCs appeared to be involved in the formation of limbal blood vessels and corneal nerve fibers. These data clearly revealed that MCs participate in the development of the murine cornea.