Plant-derived biomass-based hydrogels for biomedical applications.

Hydrogels made of plant-derived biomass have gained popularity in biomedical applications because they are frequently affordable, readily available, and biocompatible. Finding the perfect plant-derived biomass-based hydrogels for biomedicine that can replicate essential characteristics of human tissues in regard to structure, function, and performance has proved to be difficult. In this review, we summarize some of the major contributions made to this topic, covering basic ideas and different biomass-based hydrogels made of cellulose, hemicellulose, and lignin. Also included is an in-depth discussion regarding the biosafety and toxicity assessments of biomass-based hydrogels. Finally, this review also highlights important scientific debates and major obstacles regarding biomass-based hydrogels for biomedical applications.

NADPH oxidase 1/4 dual inhibitor setanaxib suppresses platelet activation and thrombus formation.

AIMS: The production of reactive oxygen species (ROS) by NADPH oxidase (NOX) is able to induce platelet activation, making NOX a promising target for antiplatelet therapy. In this study, we examined the effects of setanaxib, a dual NOX1/4 inhibitor, on human platelet function and ROS-related signaling pathways. MATERIALS AND METHODS: In collagen-stimulated human platelets, aggregometry, assessment of ROS and Ca2+, immunoblotting, ELISA, flow cytometry, platelet adhesion assay, and assessment of mouse arterial thrombosis were performed in this study. KEY FINDINGS: Setanaxib inhibited both intracellular and extracellular ROS production in collagen-activated platelets. Additionally, setanaxib significantly inhibited collagen-induced platelet aggregation, P-selectin exposure from α-granule release, and ATP release from dense granules. Setanaxib blocked the specific tyrosine phosphorylation-mediated activation of Syk, LAT, Vav1, and Btk within collagen receptor signaling pathways, leading to reduced activation of PLCγ2, PKC, and Ca2+ mobilization. Setanaxib also inhibited collagen-induced activation of integrin αIIbß3, which is linked to increased cGMP levels and VASP phosphorylation. Furthermore, setanaxib suppressed collagen-induced p38 MAPK activation, resulting in decreased phosphorylation of cytosolic PLA2 and reduced TXA2 generation. Setanaxib also inhibited ERK5 activation, affecting the exposure of procoagulant phosphatidylserine. Setanaxib reduced thrombus formation under shear conditions by preventing platelet adhesion to collagen. Finally, in vivo administration of setanaxib in animal models led to the inhibition of arterial thrombosis. SIGNIFICANCE: This study is the first to show that setanaxib suppresses ROS generation, platelet activation, and collagen-induced thrombus formation, suggesting its potential use in treating thrombotic or cardiovascular diseases.

The role of GDF15 in attenuating noise-induced hidden hearing loss by alleviating oxidative stress.

Noise-induced hidden hearing loss (HHL) is a newly uncovered form of hearing impairment that causes hidden damage to the cochlea. Patients with HHL do not have significant abnormalities in their hearing thresholds, but they experience impaired speech recognition in noisy environments. However, the mechanisms underlying HHL remain unclear. In this study, we developed single-cell transcriptome profiles of the cochlea of mice with HHL, detailing changes in individual cell types. Our study revealed a transient threshold shift, reduced auditory brainstem response wave I amplitude, and decreased number of ribbon synapses in HHL mice. Our findings suggest elevated oxidative stress and GDF15 expression in cochlear hair cells of HHL mice. Notably, the upregulation of GDF15 attenuated oxidative stress and auditory impairment in the cochlea of HHL mice. This suggests that a therapeutic strategy targeting GDF15 may be efficacious against HHL.

Metabolic stress induces a double-positive feedback loop between AMPK and SQSTM1/p62 conferring dual activation of AMPK and NFE2L2/NRF2 to synergize antioxidant defense.

Co-occurring mutations in KEAP1 in STK11/LKB1-mutant NSCLC activate NFE2L2/NRF2 to compensate for the loss of STK11-AMPK activity during metabolic adaptation. Characterizing the regulatory crosstalk between the STK11-AMPK and KEAP1-NFE2L2 pathways during metabolic stress is crucial for understanding the implications of co-occurring mutations. Here, we found that metabolic stress increased the expression and phosphorylation of SQSTM1/p62, which is essential for the activation of NFE2L2 and AMPK, synergizing antioxidant defense and tumor growth. The SQSTM1-driven dual activation of NFE2L2 and AMPK was achieved by inducing macroautophagic/autophagic degradation of KEAP1 and facilitating the AXIN-STK11-AMPK complex formation on the lysosomal membrane, respectively. In contrast, the STK11-AMPK activity was also required for metabolic stress-induced expression and phosphorylation of SQSTM1, suggesting a double-positive feedback loop between AMPK and SQSTM1. Mechanistically, SQSTM1 expression was increased by the PPP2/PP2A-dependent dephosphorylation of TFEB and TFE3, which was induced by the lysosomal deacidification caused by low glucose metabolism and AMPK-dependent proton reduction. Furthermore, SQSTM1 phosphorylation was increased by MAP3K7/TAK1, which was activated by ROS and pH-dependent secretion of lysosomal Ca2+. Importantly, phosphorylation of SQSTM1 at S24 and S226 was critical for the activation of AMPK and NFE2L2. Notably, the effects caused by metabolic stress were abrogated by the protons provided by lactic acid. Collectively, our data reveal a novel double-positive feedback loop between AMPK and SQSTM1 leading to the dual activation of AMPK and NFE2L2, potentially explaining why co-occurring mutations in STK11 and KEAP1 happen and providing promising therapeutic strategies for lung cancer.Abbreviations: AMPK: AMP-activated protein kinase; BAF1: bafilomycin A1; ConA: concanamycin A; DOX: doxycycline; IP: immunoprecipitation; KEAP1: kelch like ECH associated protein 1; LN: low nutrient; MAP3K7/TAK1: mitogen-activated protein kinase kinase kinase 7; MCOLN1/TRPML1: mucolipin TRP cation channel 1; MEFs: mouse embryonic fibroblasts; MTORC1: mechanistic target of rapamycin kinase complex 1; NAC: N-acetylcysteine; NFE2L2/NRF2: NFE2 like bZIP transcription factor 2; NSCLC: non-small cell lung cancer; PRKAA/AMPKα: protein kinase AMP-activated catalytic subunit alpha; PPP2/PP2A: protein phosphatase 2; ROS: reactive oxygen species; PPP3/calcineurin: protein phosphatase 3; RPS6KB1/p70S6K: ribosomal protein S6 kinase B1; SQSTM1/p62: sequestosome 1; STK11/LKB1: serine/threonine kinase 11; TCL: total cell lysate; TFEB: transcription factor EB; TFE3: transcription factor binding to IGHM enhancer 3; V-ATPase: vacuolar-type H+-translocating ATPase.

Cholinium Pyridinolate Ionic Pair-Catalyzed Fixation of CO2 into Cyclic Carbonates.

A halide-free ionic pair organocatalyst was proposed for the cycloaddition of CO2 into epoxide reactions. Cholinium pyridinolate ionic pairs with three different substitution positions were designed. Under conditions of temperature of 120 °C, pressure of 1 MPa CO2, and catalyst loading of 5 mol %, the optimal catalyst cholinium 4-pyridinolate ([Ch]+[4-OP]-) was employed. After a reaction time of 12 h, styrene oxide was successfully converted into the corresponding cyclic carbonate, and its selectivity was improved to 90%. A series of terminal epoxides were converted into cyclic carbonates within 12 h, with yields ranging from 80 to 99%. The proposed mechanism was verified by 1H NMR and 13C NMR titrations. Cholinium cations act as a hydrogen bond donor to activate epoxides, and pyridinolate anions combine with carbon dioxide to form intermediate carbonate anions that attack epoxides as nucleophiles and lead to ring opening. In summary, a halide-free ionic pair organocatalyst was designed and the catalytic mechanism in the cycloaddition of CO2 into epoxides reactions was proposed.

Standard Radio-Iodine Labeling Protocols Impaired the Functional Integrity of Mesenchymal Stem/Stromal Cell Exosomes.

Mesenchymal stem/stromal cells (MSCs) are an extensively studied cell type in clinical trials due to their easy availability, substantial ex vivo proliferative capacity, and therapeutic efficacy in numerous pre-clinical animal models of disease. The prevailing understanding suggests that their therapeutic impact is mediated by the secretion of exosomes. Notably, MSC exosomes present several advantages over MSCs as therapeutic agents, due to their non-living nature and smaller size. However, despite their promising therapeutic potential, the clinical translation of MSC exosomes is hindered by an incomplete understanding of their biodistribution after administration. A primary obstacle to this lies in the lack of robust labels that are highly sensitive, capable of directly and easily tagging exosomes with minimal non-specific labeling artifacts, and sensitive traceability with minimal background noise. One potential candidate to address this issue is radioactive iodine. Protocols for iodinating exosomes and tracking radioactive iodine in live imaging are well-established, and their application in determining the biodistribution of exosomes has been reported. Nevertheless, the effects of iodination on the structural or functional activities of exosomes have never been thoroughly examined. In this study, we investigate these effects and report that these iodination methods abrogate CD73 enzymatic activity on MSC exosomes. Consequently, the biodistribution of iodinated exosomes may reflect the biodistribution of denatured exosomes rather than functionally intact ones.

Effects of myo-inositol on growth and biomarkers of environmental stress and metabolic regulation in Pacific white shrimp (Litopenaeus vannamei) reared at low salinity.

This study explored the role of myo-inositol in alleviating the low salinity stress of White Shrimp (Litopenaeus vannamei). Juvenile shrimp (0.4 ± 0.02 g) in low salinity (salinity 3) water were fed diets with myo-inositol levels of 0, 272, 518, 1020 and 1950 mg/kg (crude protein is 36.82 %, crude lipid is 7.58 %), fed shrimp in seawater at a salinity of 25 were fed a 0 mg/kg myo-inositol diet as a control (Ctrl). The experiment was carried out in tanks (50 L) with satiety feeding, and the experiment lasted for 6 weeks. After sampling, the serum was used to measure immune function, the hepatopancreas homogenate was used to measure the antioxidant capacity and hepatopancreas damage state, the hepatopancreas was used for transcriptomics analysis, and the gills were used for qPCR to measure osmotic pressure regulation. The results showed that the final weight and survival of the shrimp in the 1020 mg/kg group increased significantly compared with those in the other low salinity groups, but the final weight and biomass increase were significantly lower than those in the Ctrl group. Dietary myo-inositol improved the antioxidant capacity of shrimp under low salinity. B-cell hyperplasia and hepatic duct damage were observed in the hepatopancreas in the 0 mg/kg group. The results of transcriptome analysis showed that myo-inositol could participate in the osmotic pressure regulation of shrimp by regulating carbohydrate metabolism, amino acid metabolism, lipid metabolism and other related genes. Myo-inositol significantly affected the expression of related genes in ion transporter and G protein-coupled receptor-mediated pathways. This study demonstrated that myo-inositol can not only act as an osmotic pressure effector and participate in the osmolar regulation of shrimp through the phosphatidylinositol signaling pathway mediated by G protein-coupled receptors but also relieve low salinity stress by mediating physiological pathways such as immunity, antioxidation, and metabolism in shrimp. The binomial regression analysis of biomass increases and survival showed that the appropriate amount of myo-inositol in the L. vannamei diet was 862.50-1275.00 mg/kg under low salinity.

Genomic surveillance and evolutionary dynamics of type 2 porcine reproductive and respiratory syndrome virus in China spanning the African swine fever outbreak.

Porcine reproductive and respiratory syndrome virus (PRRSV) poses a serious threat to the pig industry in China. Our previous study demonstrated that PRRSV persists with local circulations and overseas imports in China and has formed a relatively stable epidemic pattern. However, the sudden African swine fever (ASF) outbreak in 2018 caused serious damage to China's pig industry structure, which resulted in about 40 per cent of pigs being slaughtered. The pig yields recovered by the end of 2019. Thus, whether the ASF outbreak reframed PRRSV evolution with changes in pig populations and further posed new threats to the pig industry becomes a matter of concern. For this purpose, we conducted genomic surveillance and recombination, NSP2 polymorphism, population dynamics, and geographical spread analysis of PRRSV-2, which is dominant in China. The results showed that the prevalence of ASF had no significant effects on genetic diversities like lineage composition, recombination patterns, and NSP2 insertion and deletion patterns but was likely to lead to changes in PRRSV-2 recombination frequency. As for circulation of the two major sub-lineages of Lineage 1, there was no apparent transmission of NADC30-like among provinces, while NADC34-like had obvious signs of inter-provincial transmission and foreign importation during the ASF epidemic. In addition, two suspected vaccine recombinant epidemic strains suggest a slight safety issue of vaccine use. Herein, the interference of ASF to the PRRSV-2 evolutionary pattern was evaluated and vaccine safety was analyzed, in order to monitor the potential threat of PRRSV-2 to China's pig industry in the post-epidemic era of ASF.

Towards understanding the lower CH4 selectivity of HCP-Co than FCC-Co in Fischer-Tropsch synthesis.

In Fischer-Tropsch synthesis (FTS), the cobalt catalyst has higher C5+ and lower CH4 selectivity in the hcp phase than in the fcc phase. However, a detailed explanation of the intrinsic mechanism is still missing. The underlying reason was explored combining density functional theory, Wulff construction, and a particle-level descriptor based on the slab model of surfaces that are prevalent in the Wulff shape to provide single-particle level understanding. Using a particle-level indicator of the reaction rates, we have shown that it is more difficult to form CH4 on hcp-Co than on fcc-Co, due to the larger effective barrier difference of CH4 formation and C-C coupling on hcp-Co particles, which leads to the lower CH4 selectivity of hcp-Co in FTS. Among the exposed facets of fcc-Co, the (311) surface plays a pivotal role in promoting CH4 formation. The reduction of CH4 selectivity in cobalt-based FTS is achievable through phase engineering of Co from fcc to hcp or by tuning the temperature and size of the particles.

T-2 Toxin-Mediated ß-Arrestin-1 O-GlcNAcylation Exacerbates Glomerular Podocyte Injury via Regulating Histone Acetylation.

T-2 toxin causes renal dysfunction with proteinuria and glomerular podocyte damage. This work explores the role of metabolic disorder/reprogramming-mediated epigenetic modification in the progression of T-2 toxin-stimulated podocyte injury. A metabolomics experiment is performed to assess metabolic responses to T-2 toxin infection in human podocytes. Roles of protein O-linked-N-acetylglucosaminylation (O-GlcNAcylation) in regulating T-2 toxin-stimulated podocyte injury in mouse and podocyte models are assessed. O-GlcNAc target proteins are recognized by mass spectrometry and co-immunoprecipitation experiments. Moreover, histone acetylation and autophagy levels are measured. T-2 toxin infection upregulates glucose transporter type 1 (GLUT1) expression and enhances hexosamine biosynthetic pathway in glomerular podocytes, resulting in a significant increase in ß-arrestin-1 O-GlcNAcylation. Decreasing ß-arrestin-1 or O-GlcNAc transferase (OGT) effectively prevents T-2 toxin-induced renal dysfunction and podocyte injury. Mechanistically, O-GlcNAcylation of ß-arrestin-1 stabilizes ß-arrestin-1 to activate the mammalian target of rapamycin (mTOR) pathway as well as to inhibit autophagy during podocyte injury by promoting H4K16 acetylation. To sum up, OGT-mediated ß-arrestin-1 O-GlcNAcylation is a vital regulator in the development of T-2 toxin-stimulated podocyte injury via activating the mTOR pathway to suppress autophagy. Targeting ß-arrestin-1 or OGT can be a potential therapy for T-2 toxin infection-associated glomerular injury, especially podocyte injury.

Mefenamic Acid-Upregulated Nrf2/SQSTM1 Protects Hepatocytes against Oxidative Stress-Induced Cell Damage.

Mefenamic acid (MFA) is a commonly prescribed non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory and analgesic properties. MFA is known to have potent antioxidant properties and a neuroprotective effect against oxidative stress. However, its impact on the liver is unclear. This study aimed to elucidate the antioxidative effects of MFA and their underlying mechanisms. We observed that MFA treatment upregulated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Treatment with various anthranilic acid derivative-class NSAIDs, including MFA, increased the expression of sequestosome 1 (SQSTM1) in HepG2 cells. MFA disrupted the interaction between Kelch-like ECH-associated protein 1 (Keap1) and Nrf2, activating the Nrf2 signaling pathway. SQTM1 knockdown experiments revealed that the effect of MFA on the Nrf2 pathway was masked in the absence of SQSTM1. To assess the cytoprotective effect of MFA, we employed tert-Butyl hydroperoxide (tBHP) as a ROS inducer. Notably, MFA exhibited a protective effect against tBHP-induced cytotoxicity in HepG2 cells. This cytoprotective effect was abolished when SQSTM1 was knocked down, suggesting the involvement of SQSTM1 in mediating the protective effect of MFA against tBHP-induced toxicity. In conclusion, this study demonstrated that MFA exhibits cytoprotective effects by upregulating SQSTM1 and activating the Nrf2 pathway. These findings improve our understanding of the pharmacological actions of MFA and highlight its potential as a therapeutic agent for oxidative stress-related conditions.

Peroxiredoxin V Protects against UVB-Induced Damage of Keratinocytes.

Ultraviolet B (UVB) irradiation generates reactive oxygen species (ROS), which can damage exposed skin cells. Mitochondria and NADPH oxidase are the two principal producers of ROS in UVB-irradiated keratinocytes. Peroxiredoxin V (PrxV) is a mitochondrial and cytosolic cysteine-dependent peroxidase enzyme that robustly removes H2O2. We investigated PrxV's role in protecting epidermal keratinocytes against UVB-induced ROS damage. We separated mitochondrial and cytosolic H2O2 levels from other types of ROS using fluorescent H2O2 indicators. Upon UVB irradiation, PrxV-knockdown HaCaT human keratinocytes showed higher levels of mitochondrial and cytosolic H2O2 than PrxV-expressing controls. PrxV depletion enhanced hyperoxidation-mediated inactivation of mitochondrial PrxIII and cytosolic PrxI and PrxII in UVB-irradiated keratinocytes. PrxV-depleted keratinocytes exhibited mitochondrial dysfunction and were more susceptible to apoptosis through decreased oxygen consumption rate, loss of mitochondrial membrane potential, cardiolipin oxidation, cytochrome C release, and caspase activation. Our findings show that PrxV serves to protect epidermal keratinocytes from UVB-induced damage such as mitochondrial dysfunction and apoptosis, not only by directly removing mitochondrial and cytosolic H2O2 but also by indirectly improving the catalytic activity of mitochondrial PrxIII and cytosolic PrxI and PrxII. It is possible that strengthening PrxV defenses could aid in preventing UVB-induced skin damage.

Radiolabeled Liposomes for Nuclear Imaging Probes.

Quantitative nuclear imaging techniques are in high demand for various disease diagnostics and cancer theranostics. The non-invasive imaging modality requires radiotracing through the radioactive decay emission of the radionuclide. Current preclinical and clinical radiotracers, so-called nuclear imaging probes, are radioisotope-labeled small molecules. Liposomal radiotracers have been rapidly developing as novel nuclear imaging probes. The physicochemical properties and structural characteristics of liposomes have been elucidated to address their long circulation and stability as radiopharmaceuticals. Various radiolabeling methods for synthesizing radionuclides onto liposomes and synthesis strategies have been summarized to render them biocompatible and enable specific targeting. Through a variety of radionuclide labeling methods, radiolabeled liposomes for use as nuclear imaging probes can be obtained for in vivo biodistribution and specific targeting studies. The advantages of radiolabeled liposomes including their use as potential clinical nuclear imaging probes have been highlighted. This review is a comprehensive overview of all recently published liposomal SPECT and PET imaging probes.

Association between Negative Life Events and Somatic Symptoms: A Mediation Model through Self-Esteem and Depression.

The purpose of this study was to investigate the serial multiple mediation of self-esteem and depression in the relationship between negative life events and somatic symptoms in Chinese medical students. We recruited a total of 3383 medical students for this study, and used the Patient Health Questionnaire-15 to assess the somatic symptoms of subjects; the Adolescent Self-Rating Life Events Check List to assess negative life events; the Rosenberg Self-Esteem Scale to assess self-esteem; and the Patient Health Questionnaire for depression. Descriptive analysis and statistical tests were then performed on the collected data. We showed that 39.17% of the medical students had mild somatic symptoms, 24.14% had moderate somatic symptoms, and 5.66% had severe somatic symptoms; we observed significant differences in somatic symptoms among genders, living expenses, and one-child. For negative life events, interpersonal stress was the most important predictor of somatization during the regression analysis. In addition, we observed significance for both the direct and part of the indirect paths from negative life events to somatic symptoms using mediation model analysis. However, we noted that there was no significance for the path through negative life events and self-esteem to somatic symptoms. This study revealed a high prevalence of somatic symptoms among Chinese medical students, and the findings suggested that interventions aimed at reducing somatization in this population should consider the impact of negative life events, particularly those related to interpersonal stress. One potential approach to mitigating the effects of negative life events on somatization is to enhance self-esteem and decrease the level of depression among medical students.

Temperature-Dependent Reversible Optical Properties of Mn-Based Organic-Inorganic Hybrid (C8H20N)2MnCl4 Metal Halides.

Organic-inorganic metal halides (OIMHs) have abundant optical properties and potential applications, such as light-emitting diodes, displays, solar cells, and photodetectors. Herein, we report zero-dimensional Mn-based OIMH (C8H20N)2MnCl4 single crystals synthesized by a simple slow evaporation method, which exhibit intense green emission at 520 nm originating from 4T1-6A1 transition of Mn2+ ions. Large organic cations in the crystal structure result in the isolated [MnCl4]2- tetrahedrons, and the closest Mn-Mn distance reaches 9.07 Å, which effectively inhibits the migration of excitation energy between adjacent Mn2+ emission centers, thus achieving a high quantum yield (∼87%) and a long photoluminescence (PL) lifetime (3.42 ms). The different optical and structural properties at low and high temperatures are revealed by temperature-dependent PL and X-ray diffraction spectra. The PL spectra and lifetimes under the heating and cooling processes indicate that the optical property transitions are reversible at 220/240 K. Our work provides a promising strategy for building multifunctional optoelectronic materials and insights into the understanding convertible photophysical properties from isomers of metal halides.

Mitochondrial H2O2 Is a Central Mediator of Diclofenac-Induced Hepatocellular Injury.

Nonsteroidal anti-inflammatory drug (NSAID) use is associated with adverse consequences, including hepatic injury. The detrimental hepatotoxicity of diclofenac, a widely used NSAID, is primarily connected to oxidative damage in mitochondria, which are the primary source of reactive oxygen species (ROS). The primary ROS responsible for inducing diclofenac-related hepatocellular toxicity and the principal antioxidant that mitigates these ROS remain unknown. Peroxiredoxin III (PrxIII) is the most abundant and potent H2O2-eliminating enzyme in the mitochondria of mammalian cells. Here, we investigated the role of mitochondrial H2O2 and the protective function of PrxIII in diclofenac-induced mitochondrial dysfunction and apoptosis in hepatocytes. Mitochondrial H2O2 levels were differentiated from other types of ROS using a fluorescent H2O2 indicator. Upon diclofenac treatment, PrxIII-knockdown HepG2 human hepatoma cells showed higher levels of mitochondrial H2O2 than PrxIII-expressing controls. PrxIII-depleted cells exhibited higher mitochondrial dysfunction as measured by a lower oxygen consumption rate, loss of mitochondrial membrane potential, cardiolipin oxidation, and caspase activation, and were more sensitive to apoptosis. Ectopic expression of mitochondrially targeted catalase in PrxIII-knockdown HepG2 cells or in primary hepatocytes derived from PrxIII-knockout mice suppressed the diclofenac-induced accumulation of mitochondrial H2O2 and decreased apoptosis. Thus, we demonstrated that mitochondrial H2O2 is a key mediator of diclofenac-induced hepatocellular damage driven by mitochondrial dysfunction and apoptosis. We showed that PrxIII loss results in the critical accumulation of mitochondrial H2O2 and increases the harmful effects of diclofenac. PrxIII or other antioxidants targeting mitochondrial H2O2 could be explored as potential therapeutic agents to protect against the hepatotoxicity associated with NSAID use.

Simulated vestibular spatial disorientation mouse model under coupled rotation revealing potential involvement of Slc17a6.

Spatial disorientation (SD) is the main contributor to flight safety risks, but research progress in animals has been limited, impeding a deeper understanding of the underlying mechanisms of SD. This study proposed a method for constructing and evaluating a vestibular SD mouse model, which adopted coupled rotational stimulation with visual occlusion. Physiological parameters were measured alongside behavioral indices to assess the model, and neuronal changes were observed through immunofluorescent staining. The evaluation of the model involved observing decreased colonic temperature and increased arterial blood pressure in mice exposed to SD, along with notable impairments in motor and cognitive function. Our investigation unveiled that vestibular SD stimulation elicited neuronal activation in spatially associated cerebral areas, such as the hippocampus. Furthermore, transcriptomic sequencing and bioinformatics analysis revealed the potential involvement of Slc17a6 in the mechanism of SD. These findings lay a foundation for further investigation into the molecular mechanisms underlying SD.

Radiochemical Feasibility of Mixing of 99mTc-MAA and 90Y-Microspheres with Omnipaque Contrast.

Yttrium-90 (90Y) microspheres are widely used for the treatment of liver-dominant malignant tumors. They are infused via catheter into the hepatic artery branches supplying the tumor under fluoroscopic guidance based on pre-therapy angiography and Technetium-99m macroaggregated albumin (99mTc-MAA) planning. However, at present, these microspheres are suspended in radiolucent media such as dextrose 5% (D5) solution. In order to monitor the real-time implantation of the microspheres into the tumor, the 90Y microspheres could be suspended in omnipaque contrast for allowing visualization of the correct distribution of the microspheres into the tumor. The radiochemical purity of mixing 90Y-microspheres in various concentrations of omnipaque was investigated. The radiochemical purity and feasibility of mixing 99mTc-MAA with various concentrations of a standard contrast agent were also investigated. Results showed the radiochemical feasibility of mixing 90Y-microspheres with omnipaque is radiochemically acceptable for allowing real-time visualization of radioembolization under fluoroscopy.

Genome-wide annotation of cuticular protein genes in non-biting midge Propsilocerus akamusi and transcriptome analysis of their response to heavy metal pollution.

The insect cuticle is a sophisticated chitin-protein extracellular structure for mutable functions. The cuticles varied their structures and properties in different species, and the same species but in different regions or at different stages, to fill the requirements of different functions. The alteration of cuticle structures may also be induced due to challenges by some environmental crises, such as pollution exposures. The physical properties of the cuticle were determined by the cuticle proteins (CPs) they contain. The cuticle proteins are large protein groups in all insects, which are commonly divided into different families according to their conserved protein sequence motifs. Although Chironomidae is an abundant and universal insect in global aquatic ecosystems and a popular model for aquatic toxicology, no systematic annotation of CPs was done for any species in Chironomidae before. In this work, we annotated the CP genes of Propsilocerus akamusi, the most abundant Chironomidae species in Asia. A total of 160 CP genes were identified, and 97 of them could be well classified into eight CP families: 76 CPR genes can be subdivided into three groups (further divided into three subgroups: 36 RR1 genes, 37 RR2 genes, and 3 RR3 genes), 2 CPF genes, 3 CPLCA genes, 1 CPLCG gene, 8 CPAP genes, and 3 Tweedle genes. Additionally, we analyzed the response of P. akamusi CP genes at expression level to Cu exposure, which is related to the high heavy metal tolerance and the earlier onset of pupariation in heavy metal polluted water.

Intratracheal exposure to polyhexamethylene guanidine phosphate disrupts coordinate regulation of FXR-SHP-mediated cholesterol and bile acid homeostasis in mouse liver.

A public health crisis in the form of a significant incidence of fatal pulmonary disease caused by repeated use of humidifier disinfectants containing polyhexamethylene guanidine phosphate (PHMG) recently arose in Korea. Although the mechanisms of pulmonary fibrosis following respiratory exposure to PHMG are well described, distant-organ effect has not been reported. In this study, we investigated whether intratracheal administration of PHMG affects liver pathophysiology and metabolism. Our PHMG mouse model showed a significant decrease in liver cholesterol level. An mRNA-seq analysis of liver samples revealed an alteration in the gene expression associated with cholesterol biosynthesis and metabolism to bile acids. The expression of genes involved in cholesterol synthesis was decreased in a real-time PCR analysis. To our surprise, we found that the coordinate regulation of cholesterol and bile acid homeostasis was completely disrupted. Despite the decreased cholesterol synthesis and low bile acid levels, the farnesoid X receptor/small heterodimer partner pathway, which controls negative feedback of bile acid synthesis, was activated in PHMG mice. As a consequence, gene expression of Cyp7a1 and Cyp7b1, the rate-limiting enzymes of the classical and alternative pathways of bile acid synthesis, was significantly downregulated. Notably, the changes in gene expression were corroborated by the hepatic concentrations of the bile acids. These results suggest that respiratory exposure to PHMG could cause cholestatic liver injury by disrupting the physiological regulation of hepatic cholesterol and bile acid homeostasis.