Therapeutic Efficacy of Interferon-Gamma and Hypoxia-Primed Mesenchymal Stromal Cells and Their Extracellular Vesicles: Underlying Mechanisms and Potentials in Clinical Translation.

Multipotent mesenchymal stromal cells (MSCs) hold promises for cell therapy and tissue engineering due to their self-renewal and differentiation abilities, along with immunomodulatory properties and trophic factor secretion. Extracellular vesicles (EVs) from MSCs offer similar therapeutic effects. However, MSCs are heterogeneous and lead to variable outcomes. In vitro priming enhances MSC performance, improving immunomodulation, angiogenesis, proliferation, and tissue regeneration. Various stimuli, such as cytokines, growth factors, and oxygen tension, can prime MSCs. Two classical priming methods, interferon-gamma (IFN-γ) and hypoxia, enhance MSC immunomodulation, although standardized protocols are lacking. This review discusses priming protocols, highlighting the most commonly used concentrations and durations, along with mechanisms and in vivo therapeutics effects of primed MSCs and their EVs. The feasibility of up-scaling their production was also discussed. The review concluded that priming with IFN-γ or hypoxia (alone or in combination with other factors) boosted the immunomodulation capability of MSCs and their EVs, primarily via the JAK/STAT and PI3K/AKT and Leptin/JAK/STAT and TGF-ß/Smad signalling pathways, respectively. Incorporating priming in MSC and EV production enables translation into cell-based or cell-free therapies for various disorders.

[Carbon Dioxide Mitigation Co-effect Analysis of Structural Adjustment Measures in the "2+26" Cities in the Jing-Jin-Ji Region and Its Surroundings].

The Three-Year Action Plan for Winning the Blue Sky Defense Battle states that structural adjustments of industrial, energy, transportation, and land use are important to significantly reduce CO2 and air pollutant emissions. This co-effect is evident but has not been quantified at the city-cluster level. This study developed an emission inventory for the "2+26" cities of the Jing-Jin-Ji region and its surroundings and quantitatively analyzed the impacts of measures in the Three-Year Action Plan for Winning the Blue Sky Defense Battle on the emissions of CO2 and major air pollutants using Greenhouse Gas and Air Pollution Interactions and Synergies in the "2+26" cities model (GAINS-JJJ). The results showed that in the "2+26" cities, the emission reductions in CO2, primary PM2.5, SO2, NOx, and NH3 under policy scenario 2020 were 29.1 Mt (equivalent to 2% of the emissions in 2017), 203.8 (21%), 281.8 (27%), 485.5 (17%), and 34.3 kt (3%), respectively, relative to 2017. In terms of the cities or sectors, the higher the pollutant emissions, the higher the reduction achieved. The CO2 mitigation co-effect results showed that industrial adjustment measures, such as eliminating backward production capacity, upgrades on industrial boilers, and phasing out small and polluting factories, contributed the most to the co-effect of CO2 emission reduction, whereas NOx presented the highest co-effects, with CO2 among the different air pollutants.

Mesenchymal Stromal Cell Mitochondrial Transfer as a Cell Rescue Strategy in Regenerative Medicine: A Review of Evidence in Preclinical Models.

Mesenchymal stromal cells (MSC) have excellent clinical potential and numerous properties that ease its clinical translation. Mitochondria play a crucial role in energy metabolism, essential for cellular activities, such as proliferation, differentiation, and migration. However, mitochondrial dysfunction can occur due to diseases and pathological conditions. Research on mitochondrial transfer from MSCs to recipient cells has gained prominence. Numerous studies have demonstrated that mitochondrial transfer led to increased adenosine triphosphate (ATP) production, recovered mitochondrial bioenergetics, and rescued injured cells from apoptosis. However, the complex mechanisms that lead to mitochondrial transfer from healthy MSCs to damaged cells remain under investigation, and the factors contributing to mitochondrial bioenergetics recovery in recipient cells remain largely ambiguous. Therefore, this review demonstrates an overview of recent findings in preclinical studies reporting MSC mitochondrial transfer, comprised of information on cell sources, recipient cells, dosage, route of administration, mechanism of transfer, pathological conditions, and therapeutic effects. Further to the above, this research discusses the potential challenges of this therapy in its clinical settings and suggestions to overcome its challenges.

Combination Treatment With Remdesivir and Ivermectin Exerts Highly Synergistic and Potent Antiviral Activity Against Murine Coronavirus Infection.

The recent COVID-19 pandemic has highlighted the urgency to develop effective antiviral therapies against the disease. Murine hepatitis virus (MHV) is a coronavirus that infects mice and shares some sequence identity to SARS-CoV-2. Both viruses belong to the Betacoronavirus genus, and MHV thus serves as a useful and safe surrogate model for SARS-CoV-2 infections. Clinical trials have indicated that remdesivir is a potentially promising antiviral drug against COVID-19. Using an in vitro model of MHV infection of RAW264.7 macrophages, the safety and efficacy of monotherapy of remdesivir, chloroquine, ivermectin, and doxycycline were investigated. Of the four drugs tested, remdesivir monotherapy exerted the strongest inhibition of live virus and viral RNA replication of about 2-log10 and 1-log10, respectively (at 6 µM). Ivermectin treatment showed the highest selectivity index. Combination drug therapy was also evaluated using remdesivir (6 µM) together with chloroquine (15 µM), ivermectin (2 µM) or doxycycline (15 µM) - above their IC50 values and at high macrophage cell viability of over 95%. The combination of remdesivir and ivermectin exhibited highly potent synergism by achieving significant reductions of about 7-log10 of live virus and 2.5-log10 of viral RNA in infected macrophages. This combination also resulted in the lowest cytokine levels of IL-6, TNF-α, and leukemia inhibitory factor. The next best synergistic combination was remdesivir with doxycycline, which decreased levels of live virus by ~3-log10 and viral RNA by ~1.5-log10. These results warrant further studies to explore the mechanisms of action of the combination therapy, as well as future in vivo experiments and clinical trials for the treatment of SARS-CoV-2 infection.

The solvent-induced isomerization of silver thiolate clusters with symmetry transformation.

A novel ligand-stabilized Ag12 nanocluster was synthesized as a model cluster to investigate the solvent-induced isomerization of Ag12 clusters. Another two novel Ag12 clusters as well as their related symmetry transformations were also successfully obtained through the above solvent-induced isomerization process.

An Anionic Nanotubular Metal-Organic Framework for High-Capacity Dye Adsorption and Dye Degradation in Darkness.

A metal-organic framework (MOF), named SCNU-Z2, based on a new heterotopic tripodal nitrogen-containing ligand, has been constructed. Due to the replacement of one imidazole group in the reported ligand with one tetrazole group, the charge of the framework is changed from cationic to anionic but retains the same framework structure. The framework consists of tubular channels with a diameter of 1.5 nm and exhibits satisfactory stability in water with a pH range of 3-11. The anionic nature of the framework allows the effective adsorption of the cationic dyes MLB, CV, and RhB with capacities of 455.6, 847.4, and 751.8 mg/g, respectively. Among them, the adsorption capacities for SCNU-Z2 on CV and RhB rank as the highest when compared with other reported MOFs. In contrast, SCNU-Z2 exhibits an extremely low capacity for anionic dyes MO and AO, making it useful for the separation of anionic and cationic dyes based on a charge-dependent mode. Interestingly, SCNU-Z2 can be used to degrade an anionic dye, MB, within 30 min under darkness at room temperature. The apparent activation energy of the dye degradation reaction is calculated to be approximately 18.96 kJ·mol-1, implying that the catalytic reaction of MB can be considered as a low-temperature thermocatalytic reaction in the dark/SCNU-Z2 system.

A cationic [Ag12S12] cluster-based 2D coordination polymer and its dye composite with enhanced photocurrent and dielectric responses.

A cationic two-dimensional coordination polymer sustained by a [Ag12S12] cluster secondary building unit has been prepared from a stepwise solid-state reaction. This coordination polymer is capable of associating the anionic dye Congo Red, yielding a composite material that exhibits improved photocurrent and dielectric responses as compared to the pristine polymer.