Organs Of Mice Research Articles

Synthesis and evaluation of fluorinated piperazine‐hydroxyethylamine analogues as potential antiplasmodial candidates

In this manuscript, twenty‐one novel fluorinated piperazine‐hydroxyethylamine analogues were synthesized and tested against Plasmodium falciparum (Pf). Among tested compounds, two 13g and 14g exhibited promising inhibitory activity on Pf3D7 with IC50 values of 0.28 and 0.09 µM, respectively. Neither of the hits exhibited cytotoxicity on HepG2 cells up to 150 µM and Vero cells up to 20 µM. Compounds 13g and 14g were also evaluated against chloroquine‐resistant PfDd2 and displayed IC50 values of 0.11 and 0.10 µM, respectively. Next, 13g and 14g were administered to the Plasmodium berghei mice model at 30mg/kg intraperitoneally for four consecutive doses, which showed 25% and 50% reduction in the parasitemia load, respectively. The efficacy of hits 13g and 14g was improved along with mean survival time when administered in combination with artesunate. On liver‐stage parasites, compounds 13g and 14g showed >90% inhibition at 1µM. Compound 14g was also tested for toxicity in mice at 100 mg/kg dose, which revealed no abnormality in mice organs. Preliminary pharmacokinetic studies of compound 14g exhibited absorption and maintained a presence in the body for more than six hours.

STEMIN and YAP5SA, the future of heart repair?

This review outlines some of the many approaches taken over a decade or more to repair damaged hearts. We showcase the recent breakthroughs in organ regeneration elicited by reprogramming factors OCT3/4, SOX2, KLF4, and C-MYC (OKSM). Transient OKSM transgene expression rejuvenated senescent organs in mice. OKSM transgenes also caused murine heart cell regeneration. A triplet alanine mutation of the N-terminus of Serum Response Factor’s MADS box SRF153(A3), termed STEMIN, and the YAP mutant, YAP5SA synergized and activated OKSM and NANOG in adult rat cardiac myocytes; thus, causing rapid nuclear proliferation and blocked myocyte differentiation. In addition, ATAC seq showed induced expression of growth factor genes FGFs, BMPs, Notchs, IGFs, JAK, STATs and non-canonical Wnts. Injected STEMIN and YAP5SA synthetic modifying mRNA (mmRNA) into infarcted adult mouse hearts, brought damaged hearts back to near normal contractility without severe fibrosis. Thus, STEMIN and YAP5SA mmRNA may exert additional regenerative potential than OKSM alone for treating heart diseases.

Mapping of β3-Adrenergic Receptor in Living Cells with a Ligand-Guided Fluorescent Probe.

Tracking the dynamic distribution of native proteins in living cells or tissues in real time is essential for understanding the functional mechanisms involved in their physiological or pathological processes. The β3-adrenergic receptor (β3-AR) has important biological functions. It is expected to be a diagnostic indicator for aging, yet current probes for β-ARs are unable to dynamically monitor β3-AR in real time, which impedes the progress of β3-AR research. Here, we developed a ligand-directed anchoring probe, β3-ARP, that precisely covalently anchors with native β3-AR in living cells, for the diagnosis of senescence. The ligand-directed anchoring probe selectively recognizes and traces β3-AR and can achieve dynamic observation and monitoring of β3-AR in living cells, including the interaction between lipid droplets and mitochondria. Moreover, we were able to directly probe the distribution of β3-AR in various organs of aging mice in situ and track the location of native β3-AR in different types of primary neuronal cells using β3-ARP and two-photon imaging, which revealed the aberrant accumulation of lipid droplets and the distribution of β3-AR in neurological diseases. This research has resulted in a new covalently anchoring fluorescent probe, β3-ARP, which could serve as a powerful tool to explore the link between β3-AR and age-related diseases.

5′-tRNAGly(GCC) halves generated by IRE1α are linked to the ER stress response

Transfer RNA halves (tRHs) have various biological functions. However, the biogenesis of specific 5′-tRHs under certain conditions remains unknown. Here, we report that inositol-requiring enzyme 1α (IRE1α) cleaves the anticodon stem-loop region of tRNAGly(GCC) to produce 5′-tRHs (5′-tRH-GlyGCC) with highly selective target discrimination upon endoplasmic reticulum (ER) stress. Levels of 5′-tRH-GlyGCC positively affect cancer cell proliferation and modulate mRNA isoform biogenesis both in vitro and in vivo; these effects require co-expression of two nuclear ribonucleoproteins, HNRNPM and HNRNPH2, which we identify as binding proteins of 5′-tRH-GlyGCC. In addition, under ER stress in vivo, we observe simultaneous induction of IRE1α and 5′-tRH-GlyGCC expression in mouse organs and a distantly related organism, Cryptococcus neoformans. Thus, collectively, our findings indicate an evolutionarily conserved function for IRE1α-generated 5′-tRH-GlyGCC in cellular adaptation upon ER stress.

Intra-specific variations in Schistosoma mansoni and their possible contribution to inconsistent virulence and diverse clinical outcomes.

Schistosoma mansoni was introduced from Africa to the Americas during the transatlantic slave trade and remains a major public health problem in parts of South America and the Caribbean. This study presents a comprehensive comparative analysis of three S. mansoni strains with different geographical origins-from Liberia, Belo Horizonte and Puerto Rico. We demonstrated significant variation in virulence and host-parasite interactions. We investigated the phenotypic characteristics of the parasite and its eggs, as well as the immunopathologic effects on laboratory mouse organ systems. Our results show significant differences in worm morphology, worm burden, egg size, and pathologic organ changes between these strains. The Puerto Rican strain showed the highest virulence, as evidenced by marked liver and spleen changes and advanced liver fibrosis indicated by increased collagen content. In contrast, the strains from Liberia and Belo Horizonte had a less pathogenic profile with less liver fibrosis. We found further variations in granuloma formation, cytokine expression and T-cell dynamics, indicating different immune responses. Our study emphasizes the importance of considering intra-specific variations of S. mansoni for the development of targeted therapies and public health strategies. The different virulence patterns, host immune responses and organ pathologies observed in these strains provide important insights for future research and could inform region-specific interventions for schistosomiasis control.

Genetic framework sequencing analysis of Candida tropicalis in dairy cow mastitis and study of pathogenicity and drug resistance

Candida tropicalis (C. tropicalis) is a zoonotic pathogen that is widespread in the environment and in recent years an increasing number of dairy cows have been infected with the fungus causing mastitis in cows.In this study, 37 milk samples from the udders of cows with clinical mastitis were collected from a dairy farm in Guangxi Province, China, from which C. tropicalis was isolated and identified, and then the isolated fungi were subjected to genome frame map sequencing, genome functional analysis as well as comparative genome analysis of the sequencing results, and combined with the virulence test of the fungi and drug sensitivity test of the fungi determined in infected mice, the resistance genes and pathogenicity of the fungi were Analysis of resistance genes and pathogenicity.Our study results revealed the isolation and characterisation of C. tropicalis from diseased cows, with a genome length of approximately 14.27 Mb. Functional annotation of the genome identified 4068 genes associated with C. tropicalis. The strain exhibited a chemoresistance mutation in the gene cyp51,a virulence-enhancing mutation in the gene VTC4, and mutations in genes linked to drug resistance. Pathogenicity tests demonstrated that C. tropicalis could induce damage to the internal organs of mice, leading to different levels of cyanosis in the abdominal cavity, white necrotic foci on the surface of internal organs, lung hemorrhage, and enlargement of the spleen and thymus.Histological sections also revealed varying degrees of hemorrhage and degenerative changes in the cells of different organs in the mice. Drug sensitivity tests showed that the fungus was highly sensitive to nystatin and ketoconazole, moderately sensitive to amphotericin B, and insensitive to antibiotics such as itraconazole, gentamicin, and penicillin. In conclusion, C. tropicalis isolated from dairy cows in the Guangxi region in this study was pathogenic and resistant to azoles such as itraconazole and fluconazole, and this study provides a theoretical basis for the further screening of novel resistance genes in C. tropicalis, as well as providing a certain reference for the drugs used for the treatment of fungal cow mastitis in this region.

Structural Engineering of Cationic Block Copolymer Architectures for Selective Breaching of Prokaryotic and Eukaryotic Biological Species.

Positively charged antimicrobial polymers are known to cause severe damage to biological systems, and thus synthetic strategies are urgently required to design next-generation nontoxic cationic macromolecular architectures for healthcare applications. Here, we report a structural-engineering strategy to build cationic linear and star-block copolymer nanoarchitectures having identical chemical composition, molar mass, nanoparticle size, and positive surface charge, yet they differ distinctly in their biological action in breaching prokaryotic species such as E. coli (Gram-negative bacteria) without affecting eukaryotic species like red-blood and mammalian cells. For this purpose, linear and star-block structures are built on a polycaprolactone biodegradable platform having an imidazolium positive handle. Under physiological conditions, the linear architecture exhibits toxicity indiscriminately to all biological species, whereas its star counterpart is remarkably selective in membrane breaching action toward bacteria while maintaining inertness toward eukaryotic species. Confocal microscopy analysis of HPTS fluorescent dye-loaded star-polymer nanoparticles substantiated their antimicrobial action in E. coli. Tissue-penetrable near-infrared fluorescent dye (IR-780) loaded NP aided the in vivo biodistribution analysis and ex vivo quantification of cationic species' accumulations in vital organs in mice. Azithromycin, a clinical water-insoluble macrolide, is delivered from the star platform to accomplish synergistic antimicrobial activity by the combination of bactericidal-bacteriostatic action of the polymer carrier and drug together in a single system.

Manifestation of polystyrene microplastic accumulation in brain with emphasis on morphometric and histopathological changes in limbic areas of Swiss albino mice

The widespread problem of microplastic (MP) contamination is becoming a major threat to the globe. Although most of the research to date has concentrated on the physiological impacts of MPs exposure, a relatively new field of study is beginning to examine its effects on the behaviour and limbic regions of the brain. In this study, exposure to polystyrene MPs (PS-MPs) for acute and sub-chronic durations negatively affected cognition and induced anxiety-like behaviour in mice. PS-MPs were detected in vital organs of mice, including the brain, which induced neurobehavioural and pathological changes in the limbic system. Furthermore, morphometric analysis revealed a significant decrease in the total cell count in the Dentate Gyrus (DG) and Cornu Ammonis (CA) regions of the hippocampus. Signs of neuronal injury and dystrophic changes were observed in the cortex, amygdala, and hypothalamus, potentially affecting anxiety and fear responses. Our study thus provides insight into the effect of PS-MPs on the neurobiology of the brain’s limbic system and related behavioural alterations.

Hypothalamic representation of the imminence of predator threat detected by the vomeronasal organ in mice.

Animals have the innate ability to select optimal defensive behaviors with appropriate intensity within specific contexts. The vomeronasal organ (VNO) serves as a primary sensory channel for detecting predator cues by relaying signals to the medial hypothalamic nuclei, particularly the ventromedial hypothalamus (VMH), which directly controls defensive behavioral outputs. Here, we demonstrate that cat saliva contains predator cues that signal the imminence of predator threat and modulate the intensity of freezing behavior through the VNO in mice. Cat saliva activates VNO neurons expressing the V2R-A4 subfamily of sensory receptors, and the number of VNO neurons activated in response to saliva correlates with both the freshness of saliva and the intensity of freezing behavior. Moreover, the number of VMH neurons activated by fresh, but not old, saliva positively correlates with the intensity of freezing behavior. Detailed analyses of the spatial distribution of activated neurons, as well as their overlap within the same individual mice, revealed that fresh and old saliva predominantly activate distinct neuronal populations within the VMH. Collectively, this study suggests that there is an accessory olfactory circuit in mice that is specifically tuned to time-sensitive components of cat saliva, which optimizes their defensive behavior to maximize their chance of survival according to the imminence of threat.

Hypothalamic representation of the imminence of predator threat detected by the vomeronasal organ in mice

Animals have the innate ability to select optimal defensive behaviors with appropriate intensity within specific contexts. The vomeronasal organ (VNO) serves as a primary sensory channel for detecting predator cues by relaying signals to the medial hypothalamic nuclei, particularly the ventromedial hypothalamus (VMH), which directly controls defensive behavioral outputs. Here, we demonstrate that cat saliva contains predator cues that signal the imminence of predator threat and modulate the intensity of freezing behavior through the VNO in mice. Cat saliva activates VNO neurons expressing the V2R-A4 subfamily of sensory receptors, and the number of VNO neurons activated in response to saliva correlates with both the freshness of saliva and the intensity of freezing behavior. Moreover, the number of VMH neurons activated by fresh, but not old, saliva positively correlates with the intensity of freezing behavior. Detailed analyses of the spatial distribution of activated neurons, as well as their overlap within the same individual mice, revealed that fresh and old saliva predominantly activate distinct neuronal populations within the VMH. Collectively, this study suggests that there is an accessory olfactory circuit in mice that is specifically tuned to time-sensitive components of cat saliva, which optimizes their defensive behavior to maximize their chance of survival according to the imminence of threat.

Sex and organ specific proteomic responses to vitamin C deficiency in the brain, heart, liver, and spleen of Gulo-/- mice.

Recent advances in mass spectrometry have indicated that the water-soluble antioxidant vitamin C differentially modulates the abundance of various proteins in the hepatic tissue of female and male mice. In this study, we performed LC-MS/MS to identify and quantify proteins that correlate with serum vitamin C concentrations in the whole brain, heart, liver, and spleen tissues in mice deficient for the enzyme L-Gulonolactone oxidase required for vitamin C synthesis in mammals. This work shows for the first time that various biological processes affected by a vitamin C deficiency are not only sex specific dependent but also tissue specific dependent even though many proteins have been identified and quantified in more than three organs. For example, the abundance of several complex III subunits of the mitochondrial electron transport chain correlated positively with the levels of serum vitamin C only in the liver and not in the other tissues examined in this study even though such proteins were identified in all the organs analyzed. Western blot analyses on the Uqcrc1 and Uqcrfs1 complex III subunits validated the mass spectrometry results. Interestingly, the ferritin subunits represented the few quantified protein complexes that correlated positively with serum vitamin C in all the organs examined. Concomitantly, serum ferritin light chain 1 was inversely correlated with vitamin C levels in the serum. Thus, our study provides an initial comprehensive atlas of proteins significantly correlating with vitamin C in four organs in mice that will be a useful resource to the scientific community.

Pathogenicity of psychrotolerant strains of Antarctic Pseudogmynoascus fungi reveals potential opportunistic profiles

Recent studies have demonstrated the presence of fungal taxa in the extreme ecosystems of Antarctica that are known to opportunistically infect humans and animals. Among these are members of the genus Pseudogymnoascus, including some that are genetically similar to P. destructans, known to be pathogenic to bats. We evaluated the in vitro and in vivo pathogenic potential of 11 Pseudogymnoascus spp. strains recovered from Antarctica. All strains were able to grow at temperatures up to 28 °C and displayed in vitro pathogenicity through hemolytic activity, growth at different pH levels, production of hydrolytic enzymes, spore diameters, tolerance to oxidative stress, hypoxia, and halotolerance. Among them, Pseudogymnoascus sp. UFMG 8532 exhibited strong in vitro pathogenicity and in preliminary in vivo assay killed 100 % of Tenebrio molitor larvae within one day. The pathogenicity of the same strain was also tested using immunosuppressed BALB/c mouse models. Survival of BALB/c mice was affected, with oscillations between weight gain and loss, and impacts on sensory function, reflexes and autonomic function. Histopathological data from the organs of infected mice showed evidence of inflammatory processes, with numerous neutrophils, a small number of macrophages, fluid accumulation inside the lungs and intense hyperemia. Our results indicate that Antarctic Pseudogymnoascus spp. strains obtained from various substrates/habitats in maritime Antarctica may possess intrinsic virulence factors and pathogenic potential for immunosuppressed animals and humans in the region. Given that the Antarctic environment is an important reservoir for Pseudogymnoascus species, which display growth performance across a range of temperatures, it is possible that increasing temperatures in the maritime Antarctic could activate dormant genes or biochemical pathways, select virulent species and/or strains, and facilitate their spread within and beyond the region. The ability of Pseudogymnoascus species to grow slowly even at 28°C, coupled with their potential in vitro and in vivo virulence factors, suggests that these fungi might be undergoing an opportunistic transition due to the effects of climate change on the Antarctic Peninsula.

Effect of primary copper metabolism disturbance on elemental, protein, and lipid composition of the organs in Jackson toxic milk mouse.

Toxic milk (txJ) is an autosomal recessive mutation in the Atp7b gene in the C3H/HeJ strain, observed at The Jackson Laboratory in Maine, USA. TxJ mice exhibit symptoms similar to those of human Wilson's disease (WD). The study aimed to verify organ involvement in a mouse model of WD. TxJ mice and control animals were sacrificed at 2, 4, 8, and 14months of age. Total X-ray Fluorescence Spectroscopy (TXRF) was used to determine the elemental concentration in organs. Tissue chemical composition was measured by Fourier Transform Infrared Spectroscopy (FTIR). Additionally, hybrid mapping of FTIR and microXRF was performed. Elevated concentrations of Cu were observed in the liver, striatum, eye, heart, and duodenum of txJ mice across age groups. In the striatum of the oldest txJ mice, there was lower lipid content and a higher fraction of saturated fats. The secondary structure of striatum proteins was disturbed in txJ mice. In the livers of txJ mice, higher concentrations of saturated fats and disturbances in the secondary structure of proteins were observed. The concentration of neurofilaments was significantly higher in txJ serum. The distribution of Cu deposits in brains was uniform with no prevalence in any anatomic structure in either group, but significant protein structure changes were observed exclusively in the striatum of txJ. In this txJ animal model of WD, pathologic copper accumulation occurs in the duodenum, heart, and eye tissues. Increased copper concentration in the liver and brain results in increased saturated fat content and disturbances in secondary protein structure, leading to hepatic injury and neurodegeneration.

Cadmium-induced lung injury disrupts immune cell homeostasis in the secondary lymphoid organs in mice

Cadmium is a well-known toxic heavy metal that poses significant health risks, particularly through inhalation, smoking, and the consumption of contaminated food. Exposure to cadmium is linked to the development and exacerbation of chronic lung diseases such as pulmonary fibrosis and chronic obstructive pulmonary disease (COPD). This study investigated the systemic effects of intratracheal cadmium chloride (0.5mg/kg) instillation in C57BL/6 mice. All parameters, including inflammation assessment, lung function evaluation (using Flexi-vent), and immunophenotyping of T-cells in secondary lymphoid organs (spleen and mediastinal lymph nodes), were analyzed 14 days after Cd exposure. The results demonstrated that cadmium exposure led to significant immune cell infiltration in bronchoalveolar lavage (BAL) fluid, altered pro-inflammatory cytokine levels, and was associated with impaired lung function, characterized by increased lung resistance and Newtonian resistance. Analysis of T-cell populations revealed no significant changes in total T-cells in mediastinal lymph nodes and spleen, but a decrease in CD4+ T-cells and an increase in CD8+ T-cells were observed. These findings suggest that cadmium disrupts T-cell homeostasis in secondary lymphoid organs. Further research is crucial to elucidate the mechanisms underlying cadmium-induced lung injury and immune dysregulation, essential for developing effective therapeutic interventions against chronic lung diseases caused by cadmium exposure.

Synergistic chemo-photothermal anticancer effect of pH-responsive curcumin loaded mesoporous silica decorated reduced graphene

Synergistic chemo-photothermal therapy is employed to treat cancer. In this work, the curcumin loaded mesoporous silica on reduced graphene oxide (Cur-mSiO2@rGO) is synthesized. The mSiO2@rGO nanocarrier combines rGO to absorb NIR radiations with mSiO2 to load the drug. The mSiO2@rGO thus functions as bimodal photothermal agent and pH-responsive drug nanocarrier. Curcumin loaded onto the nanocarrier possesses antiproliferative, antioxidant, anti-inflammatory, pro-apoptotic, and antiangiogenic characteristics. It has anticancer potential against malignancies of stomach, liver, breast, lungs, and prostate. Breast cancer (BCa) is a major health concern worldwide. Curcumin inhibits BCa by mechanisms including apoptosis, cell cycle arrest, and modulation of signaling pathways. Moreover, curcumin blocks transcription factor (NF-κB), PI3K/AKT signaling, and STAT3 protein to inhibit liver cancer cell growth and survival. Cur-mSiO2@rGO targets cancer cells with enhanced loading capacity of 92 ± 1.02 % curcumin which is specifically released in the acidic tumor environment. NIR lamp irradiation at 808 nm ablates cancer cells to demonstrate the high photothermal conversion efficiency of rGO. In vitro experiments prove that synergistic chemo-photothermal therapy effectively kills cancer cells (HepG2 and MCF-7) compared to the single chemotherapeutic treatment. The toxicity of Cur-mSiO2@rGO is analyzed in vivo by the serum biochemical analysis, and biosafety by histopathological examination of vital body organs. A 1000 mg/kg specific dose of Cur-mSiO2@rGO shows no toxic effect on mice organs. Additionally, the in vivo studies confirm that Cur-mSiO2@rGO with NIR reduces tumor growth. Therefore, the multifunctional Cur-mSiO2@rGO can be a safe chemopreventive nanocarrier in tumor management and cancer photothermal therapy.

OrganogenesisDB: A Comprehensive Database Exploring the Cell-Type Identities and Gene Expression Dynamics during Organogenesis.

Organogenesis,the phase ofembryonic developmentthat starts at the end ofgastrulationand continues untilbirth is the critical process for understanding cellular differentiation and maturation during organ development. The rapid development of single-cell transcriptomics technology has led to many novel discoveries in understanding organogenesis while also accumulating a large quantity of data. To fill this gap, OrganogenesisDB (http://organogenesisdb.com/), which is a comprehensive database dedicated to exploring cell-type identification and gene expression dynamics during organogenesis, is developed. OrganogenesisDB contains single-cell RNA sequencing data for more than 1.4 million cells from 49 published datasets spanning various developmental stages. Additionally, 3324 cell markers are manually curated for 1120 cell types across 9 human organs and 4 mouse organs. OrganogenesisDB leverages various analysis tools to assist users in annotating and understanding cell types at different developmental stages and helps in mining and presenting genes that exhibit specific patterns and play key regulatory roles during cell maturation and differentiation. This work provides a critical resource and useful tool for deciphering cell lineage determination and uncovering the mechanisms underlying organogenesis.

Cold Exposure Alleviates T2DM Through Plasma-Derived Extracellular Vesicles.

Anecdotal reports have praised the benefits of cold exposure, exemplified by activities like winter swimming and cold water immersion. Cold exposure has garnered acclaim for its potential to confer benefits and potentially alleviate diabetes. We posited that systemic cold temperature (CT, 4-8°C) likely influences the organism's blood components through ambient temperature, prompting our investigation into the effects of chronic cold exposure on type 2 diabetic (T2DM) mice and our initial exploration of how cold exposure mitigates the incidence of T2DM. The effects of CT (4-8°C) or room temperature (RT, 22-25°C) on T2DM mice were investigated. Mice blood and organ specimens were collected for fully automated biochemical testing, ELISA, HE staining, immunohistochemistry, and immunofluorescence. Glucose uptake was assessed using flow cytometry with 2-NBDG. Changes in potential signaling pathways such as protein kinase B (AKT), phosphorylated AKT (p-AKT), insulin receptor substrates 1 (IRS1), and phosphorylated IRS1 (p-IRS1) were evaluated by Western blot. CT or CT mice plasma-derived extracellular vesicles (CT-EVs) remarkably reduced blood glucose levels and improved insulin sensitivity in T2DM mice. This treatment enhanced glucose metabolism, systemic insulin sensitivity, and insulin secretion function while promoting glycogen accumulation in the liver and muscle. Additionally, CT-EVs treatment protected against the streptozocin (STZ)-induced destruction of islets in T2DM mice by inhibiting β-cell apoptosis. CT-EVs also shielded islets from destruction and increased the expression of p-IRS1 and p-AKT in adipocytes and hepatocytes. In vitro experiments further confirmed its pro-insulin sensitivity effect. Our data indicate that cold exposure may have a potentially beneficial effect on the development of T2DM, mainly through the anti-diabetic effect of plasma-derived EVs released during cold stimulation. This phenomenon could significantly contribute to understanding the lower prevalence of diabetes in colder regions.

A tau dephosphorylation-targeting chimera selectively recruits protein phosphatase-1 to ameliorate Alzheimer’s disease and tauopathies

Abnormal accumulation of hyperphosphorylated tau (pTau) is a major cause of neurodegeneration in Alzheimer's disease (AD) and related tauopathies. Therefore, reducing pTau holds therapeutic promise for these diseases. Here, we developed a chimeric peptide, named D20, for selective facilitation of tau dephosphorylation by recruiting protein phosphatase 1 (PP1) to tau. PP1 is one of the active phosphatases that dephosphorylates tau. In both cultured primary hippocampal neurons and mouse models for AD or related tauopathies, we demonstrated that single-dose D20 treatment significantly reduced pTau by dephosphorylation at multiple AD-related sites and total tau (tTau) levels were also decreased. Multiple-dose administration of D20 through tail vein injection in 3xTg AD mice effectively ameliorated tau-associated pathologies with improved cognitive functions. Importantly, at therapeutic doses, D20 did not cause detectable toxicity in cultured neurons, neural cells, or peripheral organs in mice. These results suggest that D20 is a promising drug candidate for AD and related tauopathies.

Rapid full-color serial sectioning tomography with speckle illumination and ultraviolet excitation

Three-dimensional (3D) high-resolution large-volume imaging has remained a challenge. Translational rapid ultraviolet-excited sectioning tomography (TRUST) achieves rapid and cost-effective whole-organ subcellular imaging through iterative optical scanning and mechanical sectioning. However, the axial resolution is limited by the mechanical sectioning thickness or the UV light penetration depth in tissue. Here, assisted with high-and-low-frequency (HiLo) microscopy (HiLoTRUST), the optical sectioning thickness has been reduced from tens of micrometers to ~5.8 µm. In addition, HiLoTRUST has attained a finer mechanical sectioning thickness (10–15 µm) compared to TRUST (50 µm). For high-content imaging as in TRUST, we employed two additional UV light-emitting diodes (LEDs) specifically for uniform illumination. The full-color imaging ability and improved axial resolution of HiLoTRUST have been validated by two-dimensional (2D)/3D imaging of various mouse organs and human lung cancer specimens. HiLoTRUST offers a cost-effective, full-color, and high-resolution 3D imaging approach, showing its great potential in 3D histology applications.

Haematological and Histological Effects of Nanoplastics Released from Nonfood-grade Nonwoven Polyethene Bags on Mice

Nonfood-grade nonwoven polyethene (NFWP) bags which are frequently used in microwave cooking or carrying hot foods have been reported for releasing large amount of nanoplastics. Hence, the present study was designed to investigate the harmful effects of nanoplastics released from NFWP bags on mice. NFWP bags were cut into small pieces which were then boiled in water for 5 minutes. Then the boiled water was used as nanoplastic-contaminated drinking water for treated mice for 50 days. Surprisingly, the body weights and organ weight were increased remarkably for treated mice than control mice. The total Red Blood Cell (RBC) count decreased remarkably while total WBC count increased significantly in treated mice than in control. The percentage of neutrophils decreased remarkably while percentage of Monocytes increased significantly in treated mice as compared with control. The consumption of nanoplastics caused histological damage to intestine, heart, lung, kidney and liver of treated mice. The layers of intestinal muscles in the villi of treated mice were disrupted and infiltrated with foam cells. Destruction of alveoli and fibrosis was observed in the lungs of the treated mice. The heart muscles of treated mice were also disrupted and irregularly arranged with fibrosis. In the kidney of treated mouse, enhancement of renal spaces, shrinkage of glomeruli, eroded Bowman’s capsule, deleted and congested glomeruli along with blood vessel were found. The liver of the treated mice was affected by apoptosis, fibrosis, vacuole formation in hepatocyte, congested in hepatic tissue and dilation of blood vessel. Therefore, it can be concluded that consumption of nanoplastics released from hot NFWP bags has serious deleterious effect on haematopoiesis and tissue integrity of different organs of Mice.