Generation and characterization of a humanized ACE2 mouse model to study long-term impacts of SARS-CoV-2 infection.

Although the COVID-19 pandemic has officially ended, the persistent challenge of long-COVID or post-acute COVID sequelae (PASC) continues to impact societies globally, highlighting the urgent need for ongoing research into its mechanisms and therapeutic approaches. Our team has recently developed a novel humanized ACE2 mouse model (hACE2ki) designed explicitly for long-COVID/PASC research. This model exhibits human ACE2 expression in tissue and cell-specific patterns akin to mouse Ace2. When we exposed young adult hACE2ki mice (6 weeks old) to various SARS-CoV-2 lineages, including WA, Delta, and Omicron, at a dose of 5 × 105 PFU/mouse via nasal instillation, the mice demonstrated distinctive phenotypes characterized by differences in viral load in the lung, trachea, and nasal turbinate, weight loss, and changes in pro-inflammatory cytokines and immune cell profiles in bronchoalveolar lavage fluid. Notably, no mortality was observed in this age group. Further, to assess the model's relevance for long-COVID studies, we investigated tau protein pathologies, which are linked to Alzheimer's disease, in the brains of these mice post SARS-CoV-2 infection. Our findings revealed the accumulation and longitudinal propagation of tau, confirming the potential of our hACE2ki mouse model for preclinical studies of long-COVID.

Efficient Catalytic Elimination of Chlorobenzene Based on the Water Vapor-Promoting Effect within Mn-Based Catalysts: Activity Enhancement and Polychlorinated Byproduct Inhibition.

Achieving no or low polychlorinated byproduct selectivity is essential for the chlorinated volatile organic compounds (CVOCs) degradation, and the positive roles of water vapor may contribute to this goal. Herein, the oxidation behaviors of chlorobenzene over typical Mn-based catalysts (MnO2 and acid-modified MnO2) under dry and humid conditions were fully explored. The results showed that the presence of water vapor significantly facilitates the deep mineralization of chlorobenzene and restrains the formation of Cl2 and dichlorobenzene. This remarkable water vapor-promoting effect was conferred by the MnO2 substrate, which could suitably synergize with the postconstructed acidic sites, leading to good activity, stability, and desirable product distribution of acid-modified MnO2 catalysts under humid conditions. A series of experiments including isotope-traced (D2O and H218O) CB-TPO provided complete insights into the direct involvement of water molecules in chlorobenzene oxidation reaction and attributed the root cause of the water vapor-promoting effect to the proton-rich environment and highly reactive water-source oxygen species rather than to the commonly assumed cleaning effect or hydrogen proton transfer processes (generation of active OOH). This work demonstrates the application potential of Mn-based catalysts in CVOCs elimination under practical application conditions (containing water vapor) and provides the guidance for the development of superior industrial catalysts.

Monolithic Catalyst of Ni Foam-Supported MnOx for Boosting Magnetocaloric Oxidation of Toluene.

Catalytic oxidation has been considered an effective technique for volatile organic compound degradation. Development of metal foam-based monolithic catalysts coupling electromagnetic induction heating (EMIH) with efficiency and low energy is critical yet challenging in industrial applications. Herein, a Mn18.2-NF monolithic catalyst prepared by electrodeposition exhibited superior toluene catalytic activity under EMIH conditions, and the temperature of 90% toluene conversion decreased by 89 °C compared to that in resistance furnace heating. Relevant characterizations proved that the skin effect induced by EMIH encouraged activation of gaseous oxygen, leading to superior low-temperature redox properties of Mn18.2-NF under the EMIH condition. In situ Fourier transform infrared spectroscopy results showed that skin effect-induced activation of oxidizing species further accelerated the conversion of intermediates. As a result, the Mn18.2-NF monolithic catalyst under EMIH demonstrated remarkable performance for the toluene oxidation, surpassing the conventional nonprecious metal catalyst and other reported monolithic catalysts.

Effects of bile acid metabolism on intestinal health of livestock and poultry.

Bile acids are synthesised in the liver and are essential amphiphilic steroids for maintaining the balance of cholesterol and energy metabolism in livestock and poultry. They can be used as novel feed additives to promote fat utilisation in the diet and the absorption of fat-soluble substances in the feed to improve livestock performance and enhance carcass quality. With the development of understanding of intestinal health, the balance of bile acid metabolism is closely related to the composition and growth of livestock intestinal microbiota, inflammatory response, and metabolic diseases. This paper systematically reviews the effects of bile acid metabolism on gut health and gut microbiology in livestock. In addition, our paper summarised the role of bile acid metabolism in performance and disease control.

Disclosing Support-Size-Dependent Effect on Ambient Light-Driven Photothermal CO2 Hydrogenation over Nickel/Titanium Dioxide.

The size of support in heterogeneous catalysts can strongly affect the catalytic property but is rarely explored in light-driven catalysis. Herein, we demonstrate the size of TiO2 support governs the selectivity in photothermal CO2 hydrogenation by tuning the metal-support interactions (MSI). Small-size TiO2 loading nickel (Ni/TiO2 -25) with enhanced MSI promotes photo-induced electrons of TiO2 migrating to Ni nanoparticles, thus favoring the H2 cleavage and accelerating the CH4 formation (227.7 mmol g-1 h-1 ) under xenon light-induced temperature of 360 °C. Conversely, Ni/TiO2 -100 with large TiO2 prefers yielding CO (94.2 mmol g-1 h-1 ) due to weak MSI, inefficient charge separation, and inadequate supply of activated hydrogen. Under ambient solar irradiation, Ni/TiO2 -25 achieves the optimized CH4 rate (63.0 mmol g-1 h-1 ) with selectivity of 99.8 %, while Ni/TiO2 -100 exhibits the CO selectivity of 90.0 % with rate of 30.0 mmol g-1 h-1 . This work offers a novel approach to tailoring light-driven catalytic properties by support size effect.

Niobium Boride/Graphene Directing High-Performance Lithium-Sulfur Batteries Derived from Favorable Surface Passivation.

Efficient catalysts are needed to accelerate the conversion and suppress the shuttling of polysulfides (LiPSs) to promote the further development of lithium-sulfur (Li-S) batteries. Intermetallic niobium boride (NbB2) has indefinite potential due to superior catalytic activity. Nonetheless, the lack of a rational understanding of catalysis creates a challenge for the design of catalysts. Herein, a NbB2/reduced graphene oxide-modified PP separator (NbB2/rGO/PP) is rationally designed. Essential, an in-depth insight into the catalysis mechanism of NbB2 toward LiPSs is established based on experiments and multiperspective measurement characterization, ab initio molecular dynamics (AIMD), and density functional theory (DFT). It has been uncovered that the actual catalyst that interacts with LiPSs in NbB2 is the passivated surface with an oxide layer (O2-NbB2), which occurs through B-O-Li and Nb-O-Li bonds, rather than the clean NbB2 surface. And the decomposition barrier of Li2S is greatly reduced by a substantial margin, dropping from 3.390 to 0.93 and 0.85 eV on the Nb-O and B-O surfaces, respectively, with fast Li+ diffusivity. Consequently, the cell with NbB2/rGO/PP as a functional separator achieves a high discharge capacity of 873 mAh g-1 at 1C after 100 cycles. Moreover, the benefits of NbB2/rGO/PP can be effectively maintained even at a high sulfur loading of 7.06 mg cm-2 without significant reduction and with a low electrolyte/sulfur ratio of 8 µL mg-1s. This study enhances our understanding of the catalytic mechanism of Li-S systems and presents a promising approach for developing electrocatalysts that are resilient to poisoning.

Human surfactant protein A inhibits SARS-CoV-2 infectivity and alleviates lung injury in a mouse infection model.

Introduction: SARS coronavirus 2 (SARS-CoV-2) infects human angiotensin-converting enzyme 2 (hACE2)-expressing lung epithelial cells through its spike (S) protein. The S protein is highly glycosylated and could be a target for lectins. Surfactant protein A (SP-A) is a collagen-containing C-type lectin, expressed by mucosal epithelial cells and mediates its antiviral activities by binding to viral glycoproteins. Objective: This study examined the mechanistic role of human SP-A in SARS-CoV-2 infectivity and lung injury in vitro and in vivo. Results: Human SP-A can bind both SARS-CoV-2 S protein and hACE2 in a dose-dependent manner (p<0.01). Pre-incubation of SARS-CoV-2 (Delta) with human SP-A inhibited virus binding and entry and reduced viral load in human lung epithelial cells, evidenced by the dose-dependent decrease in viral RNA, nucleocapsid protein (NP), and titer (p<0.01). We observed significant weight loss, increased viral burden, and mortality rate, and more severe lung injury in SARS-CoV-2 infected hACE2/SP-A KO mice (SP-A deficient mice with hACE2 transgene) compared to infected hACE2/mSP-A (K18) and hACE2/hSP-A1 (6A2) mice (with both hACE2 and human SP-A1 transgenes) 6 Days Post-infection (DPI). Furthermore, increased SP-A level was observed in the saliva of COVID-19 patients compared to healthy controls (p<0.05), but severe COVID-19 patients had relatively lower SP-A levels than moderate COVID-19 patients (p<0.05). Discussion: Collectively, human SP-A attenuates SARS-CoV-2-induced acute lung injury (ALI) by directly binding to the S protein and hACE2, and inhibiting its infectivity; and SP-A level in the saliva of COVID-19 patients might serve as a biomarker for COVID-19 severity.

Oleanolic acid improved intestinal immune function by activating and potentiating bile acids receptor signaling in E. coli-challenged piglets.

BACKGROUND: Infection with pathogenic bacteria during nonantibiotic breeding is one of the main causes of animal intestinal diseases. Oleanolic acid (OA) is a pentacyclic triterpene that is ubiquitous in plants. Our previous work demonstrated the protective effect of OA on intestinal health, but the underlying molecular mechanisms remain unclear. This study investigated whether dietary supplementation with OA can prevent diarrhea and intestinal immune dysregulation caused by enterotoxigenic Escherichia coli (ETEC) in piglets. The key molecular role of bile acid receptor signaling in this process has also been explored. RESULTS: Our results demonstrated that OA supplementation alleviated the disturbance of bile acid metabolism in ETEC-infected piglets (P < 0.05). OA supplementation stabilized the composition of the bile acid pool in piglets by regulating the enterohepatic circulation of bile acids and significantly increased the contents of UDCA and CDCA in the ileum and cecum (P < 0.05). This may also explain why OA can maintain the stability of the intestinal microbiota structure in ETEC-challenged piglets. In addition, as a natural ligand of bile acid receptors, OA can reduce the severity of intestinal inflammation and enhance the strength of intestinal epithelial cell antimicrobial programs through the bile acid receptors TGR5 and FXR (P < 0.05). Specifically, OA inhibited NF-κB-mediated intestinal inflammation by directly activating TGR5 and its downstream cAMP-PKA-CREB signaling pathway (P < 0.05). Furthermore, OA enhanced CDCA-mediated MEK-ERK signaling in intestinal epithelial cells by upregulating the expression of FXR (P < 0.05), thereby upregulating the expression of endogenous defense molecules in intestinal epithelial cells. CONCLUSIONS: In conclusion, our findings suggest that OA-mediated regulation of bile acid metabolism plays an important role in the innate immune response, which provides a new diet-based intervention for intestinal diseases caused by pathogenic bacterial infections in piglets.

Lymphocyte-Activation Gene 3 Facilitates Pathological Tau Neuron-to-Neuron Transmission.

The spread of prion-like protein aggregates is a common driver of pathogenesis in various neurodegenerative diseases, including Alzheimer's disease (AD) and related Tauopathies. Tau pathologies exhibit a clear progressive spreading pattern that correlates with disease severity. Clinical observation combined with complementary experimental studies has shown that Tau preformed fibrils (PFF) are prion-like seeds that propagate pathology by entering cells and templating misfolding and aggregation of endogenous Tau. While several cell surface receptors of Tau are known, they are not specific to the fibrillar form of Tau. Moreover, the underlying cellular mechanisms of Tau PFF spreading remain poorly understood. Here, it is shown that the lymphocyte-activation gene 3 (Lag3) is a cell surface receptor that binds to PFF but not the monomer of Tau. Deletion of Lag3 or inhibition of Lag3 in primary cortical neurons significantly reduces the internalization of Tau PFF and subsequent Tau propagation and neuron-to-neuron transmission. Propagation of Tau pathology and behavioral deficits induced by injection of Tau PFF in the hippocampus and overlying cortex are attenuated in mice lacking Lag3 selectively in neurons. These results identify neuronal Lag3 as a receptor of pathologic Tau in the brain，and for AD and related Tauopathies, a therapeutic target.

Human birth tissue products as a non-opioid medicine to inhibit post-surgical pain.

Pain after surgery causes significant suffering. Opioid analgesics cause severe side effects and accidental death. Therefore, there is an urgent need to develop non-opioid therapies for managing post-surgical pain. Local application of Clarix Flo (FLO), a human amniotic membrane (AM) product, attenuated established post-surgical pain hypersensitivity without exhibiting known side effects of opioid use in mice. This effect was achieved through direct inhibition of nociceptive dorsal root ganglion (DRG) neurons via CD44-dependent pathways. We further purified the major matrix component, the heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) from human AM that has greater purity and water solubility than FLO. HC-HA/PTX3 replicated FLO-induced neuronal and pain inhibition. Mechanistically, HC-HA/PTX3 induced cytoskeleton rearrangements to inhibit sodium current and high-voltage activated calcium current on nociceptive neurons, suggesting it is a key bioactive component mediating pain relief. Collectively, our findings highlight the potential of naturally derived biologics from human birth tissues as an effective non-opioid treatment for post-surgical pain and unravel the underlying mechanisms.