Permeable Bioelectronics toward Biointegrated Systems.

Bioelectronics integrates electronics with biological organs, sustaining the natural functions of the organs. Organs dynamically interact with the external environment, managing internal equilibrium and responding to external stimuli. These interactions are crucial for maintaining homeostasis. Additionally, biological organs possess a soft and stretchable nature; encountering objects with differing properties can disrupt their function. Therefore, when electronic devices come into contact with biological objects, the permeability of these devices, enabling interactions and substance exchanges with the external environment, and the mechanical compliance are crucial for maintaining the inherent functionality of biological organs. This review discusses recent advancements in soft and permeable bioelectronics, emphasizing materials, structures, and a wide range of applications. The review also addresses current challenges and potential solutions, providing insights into the integration of electronics with biological organs.

Growth of 1D Carbon Nanotube@Perovskite Core-Shell van der Waals Heterostructures through Chemical Vapor Deposition.

Perovskite is an emerging material with immense potential in the field of optoelectronics. 1D perovskite nanowires are crucial building blocks for the development of optoelectronic devices. However, producing perovskite nanowires with high quality and controlled alignment is challenging. In this study, the direct epitaxial growth of perovskite on oriented carbon nanotube (CNT) templates is presented through a chemical vapor deposition method. The deposition process of lead iodide and methylammonium iodide is systematically investigated, and a layer plus island growth mechanism is proposed to interpret the experimental observations. The aligned long CNTs serve as 1D templates and allow the growth of CNT@perovskite core-shell heterostructure with a high aspect ratio to withstand large deformation. The obtained 1D perovskite materials can be easily manipulated and transferred, enabling the facile preparation of microscale flexible devices. For proof of concept, a photodetector based on an individual CNT@methylammonium lead iodide heterostructure is fabricated. This work provides a new approach to prepare 1D hetero-nanostructure and may inspire the design of novel flexible nanophotodetectors.

The effects of nutrition education on nutritional knowledge and dietary behaviours in primary school students in Zhongshan city.

BACKGROUND: Adequate nutritional knowledge and healthy dietary behaviours are essential for promoting rational nutrition for children. However, lack of nutritional knowledge and unhealthy dietary behaviours are common among Chinese children. Therefore, we developed a school-based nutrition education (NE) program to assess its impacts on nutritional knowledge and dietary behaviours in pupils. METHODS: In this trial, one school was assigned as an intervention group (n = 199) and the other two schools were designated as a control group (n = 140). Children in the intervention group received the NE program in addition to their regular health curriculum, whereas the control group continued with their usual health curriculum without any NE program materials. RESULTS: Concerning nutritional knowledge, the mean difference (follow-up minus baseline) of average knowledge scores in the intervention group was significantly higher than that in the control group (1.99 ± 3.22 vs. 0.66 ± 3.60, p = 0.001). However, subgroup analysis revealed that this difference disappeared among boys and students with malnutrition status. Regarding dietary behaviours, the NE program significantly increased the proportion of children exhibiting high frequencies of meat and nuts consumption in the intervention group, along with diverse food choice at breakfast. Additionally, it markedly reduced the proportion of children exhibiting high frequencies of sugar-sweetened beverages and fast food consumption. Structural equation modelling analyses indicated a significant direct effect of NE intervention on nutritional knowledge and an indirect effect on dietary behaviours. CONCLUSIONS: The NE program effectively enhanced nutritional knowledge scores and further improved dietary behaviours among Chinese primary school students. Future NE programs should pay more attention to boys and children with malnutrition.

Preliminary Study on Rapid and Simultaneous Detection of Viable Escherichia coli O157:H7, Staphylococcus aureus, and Salmonella by PMA-mPCR in Food.

Escherichia coli O157:H7, Staphylococcus aureus, and Salmonella are major foodborne pathogens that are widespread in nature and responsible for several outbreaks of food safety accidents. Thus, a rapid and practical technique (PMA-mPCR) was developed for the simultaneous detection of viable E. coli O157:H7, S. aureus, and Salmonella in pure culture and in a food matrix. To eliminate false positive results, propidium monoazide (PMA) was applied to selectively suppress the DNA amplification of dead cells. The results showed the optimum concentration of PMA is 5.0 µg/mL. The detection limit of this assay by mPCR was 103 CFU/mL in the culture broth, and by PMA-mPCR was 104 CFU/mL both in pure culture and a food matrix (milk and ground beef). In addition, the detection of mixed viable and dead cells was also explored in this study. The detection sensitivity ratio of viable and dead counts was less than 1:10. Therefore, the PMA-mPCR assay proposed here might provide an efficient detection tool for the simultaneous detection of viable E. coli O157:H7, S. aureus, and Salmonella and also have great potential for the detection and concentration assessment of VBNC cells.

Kinetically Orthogonal Probe for Simultaneous Measurement of H2S and Nitroreductase: A Refined Method to Predict the Invasiveness of Tumor Cells.

The concentrations of nitroreductase and H2S have been widely used to predict the invasiveness of tumors. However, the above two substrates always interfere with the measurement of each other as both substrates react with the typical nitroaromatic probe with the same process. Moreover, the above interferences may lead to the misjudgment of the tumor invasiveness. We used a strategy combining kinetical distinguishing and signal amplification to construct a kinetically orthogonal probe labeled KOP. The above strategy expanded the gap between the reactivity of KOP to H2S and nitroreductase with an acceptable reactivity and could determine the concentration of coexisting nitroreductase and H2S on a kinetic curve with a breakpoint. KOP could also indicate the correct invasiveness tendency in the cellular model with a complex H2S generation pathway, while the traditional kinetically nonorthogonal probe could not indicate invasiveness correctly.

Fabrication of Biomaterials and Biostructures Based On Microfluidic Manipulation.

Biofabrication technologies are of importance for the construction of organ models and functional tissue replacements. Microfluidic manipulation, a promising biofabrication technique with micro-scale resolution, can not only help to realize the fabrication of specific microsized structures but also build biomimetic microenvironments for biofabricated tissues. Therefore, microfluidic manipulation has attracted attention from researchers in the manipulation of particles and cells, biochemical analysis, tissue engineering, disease diagnostics, and drug discovery. Herein, biofabrication based on microfluidic manipulation technology is reviewed. The application of microfluidic manipulation technology in the manufacturing of biomaterials and biostructures with different dimensions and the control of the microenvironment is summarized. Finally, current challenges are discussed and a prospect of microfluidic manipulation technology is given. The authors hope this review can provide an overview of microfluidic manipulation technologies used in biofabrication and thus steer the current efforts in this field.

Superior Unidirectional Water Transport and Mechanically Stable 3D Orthogonal Woven Fabric for Human Body Moisture and Thermal Management.

Unidirectional water transport performance is vital for maintaining human thermal and wet comfort in the field of garment materials. In this work, a 3D orthogonal woven fabric (3DOWF) with excellent one-way transport capacity and mechanical properties is developed via 3D weaving and plasma treatment. The 3DOWF consists of polyester yarns (first layer), cotton yarns (second layer), and viscose yarns (third layer) with successively enhanced water absorption capacity. This allows droplets to penetrate spontaneously from the hydrophobic layer to the hydrophilic layer but not vice versa. Moreover, the Coolmax yarn with the core suction effect in the Z-direction and the plasma-treated polyester of the 3DOWF are shown to efficiently speed up the water transport process. In particular, the water penetration rate of the 3DOWF reaches 25 µl s-1 . In turn, the surface temperature after water absorption is increased by 2.6 °C compared with the cotton fabric, while the tensile strengths in the weft and warp directions of the 3DOWF are 49.62 and 18 MPa, respectively. These values represent the best insulation and mechanical characteristics thus far reported among unidirectional water transport fabrics. Therefore, the 3DOWF has great potential for use in watchbands, backpack belts, insoles, and other functional textiles.

Structural insights into histone chaperone Chz1-mediated H2A.Z recognition and histone replacement.

Chz1 is a specific chaperone for the histone variant H2A.Z in budding yeast. The ternary complex formed by Chz1 and H2A.Z-H2B dimer is the major in vivo substrate of Swi2/snif2-related 1 (SWR1), the ATP-dependent chromatin remodeling enzyme that deposits H2A.Z into chromatin. However, the structural basis for the binding preference of Chz1 for H2A.Z over H2A and the mechanism by which Chz1 modulates the histone replacement remain elusive. Here, we show that Chz1 utilizes 2 distinct structural domains to engage the H2A.Z-H2B dimer for optimal and specific recognition of H2A.Z. The middle region of Chz1 (Chz1-M) directly interacts with 2 highly conserved H2A.Z-specific residues (Gly98 and Ala57) and dictates a modest preference for H2A.Z-H2B. In addition, structural and biochemical analysis show that the C-terminal region of Chz1 (Chz1-C) harbors a conserved DEF/Y motif, which reflects the consecutive D/E residues followed by a single aromatic residue, to engage an arginine finger and a hydrophobic pocket in H2A.Z-H2B, enhancing the binding preference for H2A.Z-H2B. Furthermore, Chz1 facilitates SWR1-mediated H2A.Z deposition by alleviating inhibition caused by aggregation of excess free histones, providing insights into how Chz1 controls the bioavailability of H2A.Z to assist SWR1 in promoter-specific installation of a histone mark. Our study elucidates a novel H2A.Z-recognition mechanism and uncovers a molecular rationale for binding of free histone by specialized histone chaperones in vivo.

TARS2 variants causes combination oxidative phosphorylation deficiency-21: a case report and literature review.

OBJECTIVE: To explore the clinical characteristics and genetic characteristics of the combined oxidative phosphorylation defect type 21 (COXPD21) caused by the TARS2 compound heterozygous varians, and to improve clinicians' awareness of the disease. METHODS: The clinical performance, diagnosis and treatment process and gene characteristics of COXPD21 caused by TARS2 were reviewed and analyzed and reviewed combined with the literature. RESULTS: The proband was a girl, the first birth, with repeated refractory hypokalemia, hearing impairment, developmental delay and intellectual disability，development backwardness after infection, high limb muscle tension, and increased serum lactate as the clinical phenotype. Two heterozygous varians in the TARS2 gene were detected by whole exome sequencing, one of which was c.1679(exon14) A > C (p.Asp560Ala) missense , which was derived from the mother, and the other was c.1036(exon10)C >T (p.Arg346Cys) missense variant, derived from the father, the child was diagnosed with COXPD21. The literature collected from the CNKI, Wanfang data and biomedical literature database (PubMed) until November 2021 were searched and reviewed with the key words "mitochondrial encephalomyopathy", "TARS2" and "combined oxidative phosphorylation deficiency type 21". A total of four complete domestic and foreign cases were collected from the literature search. CONCLUSION: COXPD21 onset by complex heterozygous variant of TARS2 causes refractory hypokalemia, which is rarely reported at home and abroad.

Three-Dimensional Imaging of Whole-Body Zebrafish Revealed Lipid Disorders Associated with Niemann-Pick Disease Type C1.

Imaging of lipids of whole-body specimens in two-dimensional (2D) analysis provides a global picture of the lipid changes in lipid-disturbed diseases, enabling a better understanding of lipid functions and lipid-modulation processes in different organs. However, 2D imaging of a single cross section can hardly characterize the whole-body lipid alterations. In this work, a three-dimensional matrix-assisted laser desorption/ionization mass spectrometry imaging (3D MALDI-MSI) approach was developed for analysis of whole-body zebrafish, for the first time, and applied to identify altered lipids and map their spatial distributions by using a zebrafish model of Niemann-Pick disease type C1 (NPC1), a neurovisceral lipid storage disorder causing both neurodegenerative disorder and visceral organ damage. The constructed 3D fish model provided comprehensive information on the 3D distribution of lipids of interest and allowed direct correlations between these lipids and organs of the fish. Obtained results revealed that several sphingolipids and phospholipids showed significant alterations and exhibited different localization patterns in various organs such as the brain, spinal cord, intestines, and liver-spleen region in the npc1 gene mutant fish compared to those of the wild type. The whole-body 3D MALDI-MSI approach revealed unique lipid signatures for different NPC1-affected organs, which might offer insights into the link between the impaired lipid storage and subsequent clinical symptoms, such as neurodegeneration and hepatosplenomegaly.

Biomimetic Mechanically Enhanced Carbon Nanotube Fibers by Silk Fibroin Infiltration.

Natural materials, such as silk, nacre, and bone, possess superior mechanical properties which are derived from their unique hierarchical structures. Individual carbon nanotubes (CNTs) are considered as one of the strongest materials. However, macroscopic CNT fibers usually have breaking strength far below that of individual CNTs. In this work, by mimicking the structure of natural silk fibers, strong and stiff CNT fibers are prepared by infiltrating silk fibroin (SF) into CNT fibers. There are abundant hydrogen bonds in SF, contributing to the enhanced interactions between neighboring CNTs. Glycerol is selected to promote the formation of ß-sheet conformation in SF, leading to further enhanced strength and modulus. Remarkably, the SF infiltrated CNT fibers show breaking strength of 1023 MPa, toughness of 10.3 MJ m-3 , and Young's modulus of 81.3 GPa, which are 250%, 132%, and 442% of the pristine CNT fibers. The structure of the SF and the interactions between CNTs and SF are studied via Fourier transformed infrared spectroscopy and molecular dynamics simulation. Mimicking the hierarchical structures of natural silk fibers and enhance the interfacial load transfer by infiltrating SF are effective for reinforcing CNT fibers, which may be useful in the design and preparation of other structural materials.

Sustainable Silk-Derived Multimode Carbon Dots.

Carbon dots (CDs) are widely studied for years due to their unique luminescent properties and potential applications in many fields. However, aggregation-caused quenching, monotonous emission modes, and unsustainable preparation impose restrictions on their performance and practical applications. Here, this work reports the facile synthesis of sustainable silk-derived multimode emitting CDs with dispersed-state fluorescence (DSF), aggregation-induced fluorescence (AIF), and aggregation-induced room temperature phosphorescence (AIRTP) through radiating sericin proteins in a household microwave oven (800 W, 2.5 min). The structure, luminescent properties, and the mechanism are investigated and discussed. The sericin-derived CDs have graphitized cores and heteroatom-cluster-rich surfaces. The DSF corresponds to the graphitized cores and the AIF origins from the aggregation-induced abundant orbital energy levels on the heteroatom-cluster-rich surfaces. The presence of abundant hydrogen bonds and small gap between the lowest singlet and triplet excited states induces AIRTP. Finally, based on the unique multimode emission of the prepared CDs, their applications in high-performance white-light-emitting diode, information encryption, anti-counterfeiting, and visual humidity sensors are demonstrated.

Mass Spectrometry Imaging Combined with Metabolomics Revealing the Proliferative Effect of Environmental Pollutants on Multicellular Tumor Spheroids.

Multicellular tumor spheroids (MCTS) have gained increasing attention in cancer research because they may closely mimic some physiological characteristics of solid tumors. MCTS have been considered as a useful three-dimensional cell model for evaluating the effect of exogenous molecules on tumor progression. However, little is known about the metabolic response in MCTS after exposure to exogenous molecules. Herein, we applied metabolomics combined with MALDI-mass spectrometry imaging (MSI) to investigate the proliferation of three-dimensional MDA-MB-231 breast cancer cell spheroids treated with bisphenol S (BPS). MSI data revealed that BPS, a common environmental contaminant, penetrated MCTS in 5 min and gradually localized in the core of MCTS within 4 h. Metabolomic data demonstrated that BPS exposure induced significant changes in the levels of 28 metabolites that are involved in several pathways, including purine metabolism and the tricarboxylic acid cycle. The MSI results showed that three upregulated metabolites (ATP, ADP, and AMP) acting major roles in energy supply distributed in the proliferative zone of cell spheroids, further indicating the proliferative response of MDA-MB-231 cell spheroids caused by BPS exposure. One downregulated metabolite (xanthine) associated with reactive oxidative stress was found to localize toward the inner region of cell spheroids. These MSI results demonstrated that the increase of energy supply in the outer layer of cell spheroids might be responsible for BPS-induced proliferative response. Taken together, this integrated method might offer a more accurate and intuitive assessment for the effect of exogenous molecules on cancer progression.

Preparation of Frozen Sections of Multicellular Tumor Spheroids Coated with Ice for Mass Spectrometry Imaging.

Increasing studies have utilized mass spectrometry imaging (MSI) that is a label-free tool to investigate drug penetration and drug biotransformation in multicellular tumor spheroids (MCTS). Currently, the gelatin-assisted sectioning method is widely used to prepare frozen sections of MCTS for MSI. However, owing to the limited transparency of frozen gelatin, MCTS with diameters less than 500 µm that closely mimic solid tumors are difficult to be detected when cryosectioning. In order to identify the presence of MCTS, hematoxylin and eosin staining for frozen sections and dye pretreatment for MCTS were employed in previous works, which either increased the analytical time and cost in sample preparation or caused signal suppression in sample analysis. Herein, a new sectioning method was developed to prepare MCTS frozen sections. MCTS was coated with ice to ensure good visibility for small-size MCTS. The optimal cutting temperature compound was added around the ice block to assist the formation of frozen sections. A precast frozen mold was prepared to allow the acquisition of complete MCTS frozen sections. The developed method was applied to investigate lipid distribution in MCTS by using matrix-assisted laser desorption/ionization MSI. Compared to the gelatin-assisted sectioning method, our method did not cause signal suppression and analyte delocalization. Thus, this method provides an easy, universal, and innovative strategy to prepare MCTS frozen sections for further MSI analysis. Besides, we applied our method to investigate the penetration of bisphenol A in MCTS.

Splash-Resistant and Light-Weight Silk-Sheathed Wires for Textile Electronics.

Silk has outstanding mechanical properties and biocompatibility. It has been used to fabricate traditional textiles for thousands of years and can be produced in large scale. Silk materials are potentially attractive in modern textile electronics. However, silk is not electrically conductive, thus limiting its applications in electronics. Moreover, regenerated silk is generally rigid and brittle, which hinder post processing. Here we report the fabrication of conductive silk wire in which carbon nanotube (CNT) yarns are wrapped with fluffy and flexible silk nanofiber films. The silk nanofiber film was prepared by electrospinning and then wrapped around a rotating CNT yarn in situ. The obtained silk-sheathed CNT (CNT@Silk) wire has an insulating sheath, which protects the body against electrical shock. In addition, the fabricated wires exhibit a high electrical conductivity (3.1 × 104 S/m), good mechanical strength (16 cN/tex), excellent flexibility, and high durability. More importantly, the wires have an extremely low density (2.0-7.8 × 104 g/m3), which is 2 orders of magnitude lower than that of the traditional metal wire (for example, Cu). Moreover, the wires display a good resistance to humidity, and a simple post treatment can make the wires splash-resistant, thereby expanding its applications. On the basis of these features, we demonstrate the use of the lightweight CNT@Silk wires in smart clothes, including electrochromism and near-field communication.

Genetic Stability of Parainfluenza Virus 5-Vectored Human Respiratory Syncytial Virus Vaccine Candidates after In Vitro and In Vivo Passage.

Human respiratory syncytial virus (RSV) is the leading etiologic agent of lower respiratory tract infections in children, but no licensed vaccine exists. Previously, we developed two parainfluenza virus 5 (PIV5)-based RSV vaccine candidates that protect mice against RSV challenge. PIV5 was engineered to express either the RSV fusion protein (F) or the RSV major attachment glycoprotein (G) between the hemagglutinin-neuraminidase (HN) and RNA-dependent RNA polymerase (L) genes of the PIV5 genome [PIV5-RSV-F (HN-L) and PIV5-RSV-G (HN-L), respectively]. To investigate the stability of the vaccine candidates in vitro, they were passaged in Vero cells at high and low multiplicities of infection (MOIs) for 11 generations and the genome sequences, growth kinetics, and protein expression of the resulting viruses were compared with those of the parent viruses. Sporadic mutations were detected in the consensus sequences of the viruses after high-MOI passages, and mutation rates increased under low-MOI-passage conditions. None of the mutations abolished antigen expression. Increased numbers of mutations correlated with increased growth rates in vitro, indicating that the viruses evolved through the course of serial passages. We also examined the in vivo stability of the vaccine candidates after a single passage in African green monkeys. No mutations were detected in the consensus sequences of viruses collected from the bronchoalveolar lavage (BAL) fluid of the animals. In vivo, mutations in RSV G and PIV5 L were found in individual isolates of PIV5-RSV-G (HN-L), but plaque isolates of PIV5-RSV-F (HN-L) had no mutations. To improve upon the PIV5-RSV-F (HN-L) candidate, additional vaccine candidates were generated in which the gene for RSV F was inserted into earlier positions in the PIV5 genome. These insertions did not negatively impact the sequence stability of the vaccine candidates. The results suggest that the RSV F and G gene insertions are stable in the PIV5 genome. However, the function of the foreign gene insertion may need to be considered when designing PIV5-based vaccines.IMPORTANCE The genetic stability of live viral vaccines is important for safety and efficacy. PIV5 is a promising live viral vector and has been used to develop vaccines. In this work, we examined the genetic stability of a PIV5-based RSV vaccine in vitro and in vivo We found that insertions of foreign genes, such as the RSV F and G genes, were stably maintained in the PIV5 genome and there was no mutation that abolished the expression of RSV F or G. Interestingly, the function of the inserted gene may have an impact on PIV5 genome stability.

A Single-Dose Recombinant Parainfluenza Virus 5-Vectored Vaccine Expressing Respiratory Syncytial Virus (RSV) F or G Protein Protected Cotton Rats and African Green Monkeys from RSV Challenge.

Human respiratory syncytial virus (RSV) is a common cause of severe respiratory disease among infants, immunocompromised individuals, and the elderly. No licensed vaccine is currently available. In this study, we evaluated two parainfluenza virus 5 (PIV5)-vectored vaccines expressing RSV F (PIV5/F) or G (PIV5/G) protein in the cotton rat and African green monkey models for their replication, immunogenicity, and efficacy of protection against RSV challenge. Following a single intranasal inoculation, both animal species shed the vaccine viruses for a limited time but without noticeable clinical symptoms. In cotton rats, the vaccines elicited RSV F- or G-specific serum antibodies and conferred complete lung protection against RSV challenge at doses as low as 103 PFU. Neither vaccine produced the enhanced lung pathology observed in animals immunized with formalin-inactivated RSV. In African green monkeys, vaccine-induced serum and mucosal antibody responses were readily detected, as well. PIV5/F provided nearly complete protection against RSV infection in the upper and lower respiratory tract at a dose of 106 PFU of vaccine. At the same dose levels, PIV5/G was less efficacious. Both PIV5/F and PIV5/G were also able to boost neutralization titers in RSV-preexposed African green monkeys. Overall, our data indicated that PIV5/F is a promising RSV vaccine candidate.IMPORTANCE A safe and efficacious respiratory syncytial virus (RSV) vaccine remains elusive. We tested the recombinant parainfluenza virus 5 (PIV5) vectors expressing RSV glycoproteins for their immunogenicity and protective efficacy in cotton rats and African green monkeys, which are among the best available animal models to study RSV infection. In both species, a single dose of intranasal immunization with PIV5-vectored vaccines was able to produce systemic and local immunity and to protect animals from RSV challenge. The vaccines could also boost RSV neutralization antibody titers in African green monkeys that had been infected previously. Our data suggest that PIV5-vectored vaccines could potentially protect both the pediatric and elderly populations and support continued development of the vector platform.

Influenza hemagglutinin stem-fragment immunogen elicits broadly neutralizing antibodies and confers heterologous protection.

Influenza hemagglutinin (HA) is the primary target of the humoral response during infection/vaccination. Current influenza vaccines typically fail to elicit/boost broadly neutralizing antibodies (bnAbs), thereby limiting their efficacy. Although several bnAbs bind to the conserved stem domain of HA, focusing the immune response to this conserved stem in the presence of the immunodominant, variable head domain of HA is challenging. We report the design of a thermotolerant, disulfide-free, and trimeric HA stem-fragment immunogen which mimics the native, prefusion conformation of HA and binds conformation specific bnAbs with high affinity. The immunogen elicited bnAbs that neutralized highly divergent group 1 (H1 and H5 subtypes) and 2 (H3 subtype) influenza virus strains in vitro. Stem immunogens designed from unmatched, highly drifted influenza strains conferred robust protection against a lethal heterologous A/Puerto Rico/8/34 virus challenge in vivo. Soluble, bacterial expression of such designed immunogens allows for rapid scale-up during pandemic outbreaks.

Di-2-ethylhexyl phthalate disrupts hepatic lipid metabolism in obese mice by activating the LXR/SREBP-1c and PPAR-α signaling pathways.

Di-2-ethylhexyl phthalate (DEHP), a widely utilized plasticizer, has been described as a potential obesogen based on in vivo disruption of hepatic lipid homeostasis and in vitro promotion of lipid accumulation. However, limited literature exists regarding the specific ramifications of DEHP exposure on obese individuals, and the precise mechanisms underlying the adverse effects of DEHP exposure remain unclear. This study aimed to assess the impact of DEHP on hepatic lipid metabolism in obese mice by comparing them to normal mice. Following a 10-week DEHP exposure period, the obese mice exhibited higher blood lipid levels, more severe hepatic steatosis, and more infiltrations of inflammatory cells in liver tissue than normal mice. Interestingly, the body weight of the mice exhibited no significant alteration. In addition, transcriptomic analyses revealed that both lipogenesis and fatty acid oxidation contributed to hepatic lipid metabolism dysregulation following DEHP exposure. More specifically, alterations in the transcription of genes associated with hepatic lipid metabolism were linked to the different responses to DEHP exposure observed in normal and obese mice. Additionally, the outcomes of in vitro experiments validated the in vivo findings and demonstrated that DEHP exposure could modify hepatic lipid metabolism in normal mice by activating the LXR/SREBP-1c signaling pathway to promote lipogenesis. At the same time, DEHP exposure led to inhibition of the Camkkß/AMPK pathway to suppress ß-fatty acid oxidation. Conversely, in obese mice, DEHP exposure was found to be associated with the stimulation of both lipogenesis and fatty acid oxidation via activation of the LXR/SREBP-1c and PPAR-α signaling pathways, respectively. The findings presented in this study first elucidate the contrasting mechanisms underlying DEHP-induced liver damage in obese and normal mice, thereby offering valuable insights into the pathogenesis of DEHP-induced liver damage in individuals with obesity.

In vitro and in vivo characterization of designed immunogens derived from the CD-helix of the stem of influenza hemagglutinin.

The conserved "stem" domain of influenza virus hemagglutinin (HA) is a target for broadly neutralizing antibodies and a potential vaccine antigen for induction of hetero-subtypic protection. The epitope of 12D1, a previously reported bnAb neutralizing several H3 subtype influenza strains, was putatively mapped to residues 76-106 of the CD-helix, also referred to as long alpha helix (LAH) of the HA stem. A peptide derivative consisting of wt-LAH residues 76-130 conjugated to keyhole limpet hemocyanin was previously shown to confer robust protection in mice against challenge with influenza strains of subtypes H3, H1, and H5 which motivated the present study. We report the design of multiple peptide derivatives of LAH with or without heterologous trimerization sequences and show that several of these are better folded than wt-LAH. However, in contrast to the previous study immunization of mice with wt-LAH resulted in negligible protection against a lethal homologous virus challenge, while some of the newly designed immunogens could confer weak protection. Combined with structural analysis of HA, our data suggest that in addition to LAH, other regions of HA are likely to significantly contribute to the epitope for 12D1 and will be required to elicit robust protection. In addition, a dynamic, flexible conformation of isolated LAH peptide may be required for eliciting a functional anti-viral response.