Alliance of Heart and Endoderm: Multilineage Organoids to Model Co-development.

Studies in animal models tracing organogenesis of the mesoderm-derived heart have emphasized the importance of signals coming from adjacent endodermal tissues in coordinating proper cardiac morphogenesis. Although in vitro models such as cardiac organoids have shown great potential to recapitulate the physiology of the human heart, they are unable to capture the complex crosstalk that takes place between the co-developing heart and endodermal organs, partly due to their distinct germ layer origins. In an effort to address this long-sought challenge, recent reports of multilineage organoids comprising both cardiac and endodermal derivatives have energized the efforts to understand how inter-organ, cross-lineage communications influence their respective morphogenesis. These co-differentiation systems have produced intriguing findings of shared signaling requirements for inducing cardiac specification together with primitive foregut, pulmonary, or intestinal lineages. Overall, these multilineage cardiac organoids offer an unprecedented window into human development that can reveal how the endoderm and heart cooperate to direct morphogenesis, patterning, and maturation. Further, through spatiotemporal reorganization, the co-emerged multilineage cells self-assemble into distinct compartments as seen in the cardiac-foregut, cardiac-intestine, and cardiopulmonary organoids and undergo cell migration and tissue reorganization to establish tissue boundaries. Looking into the future, these cardiac incorporated, multilineage organoids will inspire future strategies for improved cell sourcing for regenerative interventions and provide more effective models for disease investigation and drug testing. In this review, we will introduce the developmental context of coordinated heart and endoderm morphogenesis, discuss strategies for in vitro co-induction of cardiac and endodermal derivatives, and finally comment on the challenges and exciting new research directions enabled by this breakthrough.

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.

Enhancement of Mineralization Ability and Water Resistance of Vanadium-Based Catalysts for Catalytic Oxidation of Chlorobenzene by Platinum Loading.

The design of a catalyst with multifunctional sites is one of the effective methods for low-temperature catalytic oxidation of chlorinated volatile organic compounds (CVOCs). The loss of redox sites and competitive adsorption of H2O prevalent in the treatment of industrial exhaust gases are the main reasons for the weak mineralization ability and poor water vapor resistance of V-based catalysts. In this work, platinum (Pt) is selected to combine with the V/CeO2 catalyst, which provides more redox sites and H2O dissociative activation sites and further enhances its catalytic performance. The results show that PtV/CeO2 achieves 90% of the CO2 yield at 318 °C and maintains excellent catalytic activity rather than continuous deactivation within 15 h after water vapor injection. The formation of Pt-O-V bonds enhances the redox ability and promotes deep oxidation of polychlorinated intermediates, accounting for the significantly improved mineralization ability of PtV/CeO2. The dissociative activation effect of Pt on H2O molecules strengthens the migration and activation of V-adsorbed H2O, precluding V-poisoning and notably improving water resistance. This study lays a solid foundation for the efficient degradation of chlorobenzene under humid conditions.

Oleanolic acid attenuates hydrogen peroxide-induced apoptosis of IPEC-J2 cells through suppressing c-Jun and MAPK pathway.

Oleanolic acid (OA) is a natural triterpenoid with therapeutic potential for a multitude of diseases. However, the precise mechanism by which OA influences stress-induced apoptosis of intestinal epithelial cells remains elusive. Therefore, the effect of OA on intestinal diseases under stressful conditions and its possible mechanisms have been investigated. In a hydrogen peroxide (H2 O2 )-induced oxidative stress model, OA attenuated H2 O2 -induced apoptosis in a concentration-dependent manner. To investigate the underlying mechanisms, the gene expression profile of OA on IPEC-J2 cells was analyzed using an RNA sequencing system. Results from gene ontology and Kyoto encyclopedia of genes and genomes analysis confirmed that OA may mitigate the cytotoxic effects of H2 O2 by downregulating gene expression through the MAPK signaling pathway. Furthermore, Quantitative real-time polymerase chain reaction results validated the differentially expressed genes data. Western blot analysis further demonstrated that OA effectively suppressed the expression level of c-Jun protein induced by H2 O2 in IPEC-J2 cells. Collectively, our results indicate that OA pretreatment significantly attenuated H2 O2 -induced apoptosis in intestinal epithelial cells through suppressing c-Jun and MAPK pathway.

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.

Human milk oligosaccharides reduce necrotizing enterocolitis-induced neuroinflammation and cognitive impairment in mice.

Necrotizing enterocolitis (NEC) is the leading cause of morbidity and mortality in premature infants. One of the most devastating complications of NEC is the development of NEC-induced brain injury, which manifests as impaired cognition that persists beyond infancy and which represents a proinflammatory activation of the gut-brain axis. Given that oral administration of the human milk oligosaccharides (HMOs) 2'-fucosyllactose (2'-FL) and 6'-sialyslactose (6'-SL) significantly reduced intestinal inflammation in mice, we hypothesized that oral administration of these HMOs would reduce NEC-induced brain injury and sought to determine the mechanisms involved. We now show that the administration of either 2'-FL or 6'-SL significantly attenuated NEC-induced brain injury, reversed myelin loss in the corpus callosum and midbrain of newborn mice, and prevented the impaired cognition observed in mice with NEC-induced brain injury. In seeking to define the mechanisms involved, 2'-FL or 6'-SL administration resulted in a restoration of the blood-brain barrier in newborn mice and also had a direct anti-inflammatory effect on the brain as revealed through the study of brain organoids. Metabolites of 2'-FL were detected in the infant mouse brain by nuclear magnetic resonance (NMR), whereas intact 2'-FL was not. Strikingly, the beneficial effects of 2'-FL or 6'-SL against NEC-induced brain injury required the release of the neurotrophic factor brain-derived neurotrophic factor (BDNF), as mice lacking BDNF were not protected by these HMOs from the development of NEC-induced brain injury. Taken in aggregate, these findings reveal that the HMOs 2'-FL and 6'-SL interrupt the gut-brain inflammatory axis and reduce the risk of NEC-induced brain injury.NEW & NOTEWORTHY This study reveals that the administration of human milk oligosaccharides, which are present in human breast milk, can interfere with the proinflammatory gut-brain axis and prevent neuroinflammation in the setting of necrotizing enterocolitis, a major intestinal disorder seen in premature infants.

Acute Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Pregnancy Is Associated with Placental Angiotensin-Converting Enzyme 2 Shedding.

While the human placenta may be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the rate of fetal transmission is low, suggesting a barrier at the maternal-fetal interface. Angiotensin-converting enzyme (ACE)2, the main receptor for SARS-CoV-2, is regulated by a metalloprotease cleavage enzyme, a disintegrin and metalloprotease domain 17 (ADAM17). ACE2 is expressed in the human placenta, but its regulation in relation to maternal SARS-CoV-2 infection in pregnancy is not well understood. This study evaluated ACE2 expression, ADAM17 activity, and serum ACE2 abundance in a cohort of matched villous placental and maternal serum samples from control pregnancies (SARS-CoV-2 negative, n = 8) and pregnancies affected by symptomatic maternal SARS-CoV-2 infections in the second trimester [2nd Tri coronavirus disease (COVID), n = 8] and third trimester (3rd Tri COVID, n = 8). In 3rd Tri COVID compared with control and 2nd Tri COVID villous placental tissues, ACE2 mRNA expression was remarkably elevated; however, ACE2 protein expression was significantly decreased with a parallel increase in ADAM17 activity. Soluble ACE2 was also significantly increased in the maternal serum from 3rd Tri COVID infections compared with control and 2nd Tri COVID pregnancies. These data suggest that in acute maternal SARS-CoV-2 infections, decreased placental ACE2 protein may be the result of ACE2 shedding and highlights the importance of ACE2 for studies on SARS-CoV-2 responses at the maternal-fetal interface.