Assessment of stress levels and reproductive condition in giant pandas: insights from hair, faecal and saliva samples.

Concerted conservation efforts have brought the giant panda (Ailuropoda melanoleuca) back from the brink of extinction, but pandas continue to face anthropogenic threats in the wild and breeding success in captivity remains low. Because stress can have detrimental impacts on reproduction, monitoring stress- and sex-steroid levels would help assess the effectiveness of conservation mitigation measures in panda populations as well as monitor the welfare and reproductive health of captive animals. In this proof-of-concept study, we used faecal sex steroid and cortisol concentrations (n = 867 samples collected from five males and five females at Beijing Zoo every 4 days over the course of 12 months) as a reference to investigate if testosterone, estradiol, progesterone and cortisol can be meaningfully measured in panda hair (n = 10) using radio-immuno-assays. Additionally, we calculated the ratio of testosterone to cortisol (T:C ratio) for each male, which can provide a biomarker of stress and physical performance. Our findings revealed distinct monthly variations in faecal sex-steroid and cortisol concentrations, reflecting reproductive seasonality and visitor-related stress among individual pandas. Notably, the oldest male had a significantly lower T:C ratio than other males. Our results confirm that the level of sex steroids and cortisol can be assayed by panda hair, and the hair cortisol concentrations correlate significantly with that in faeces with one month lag behind (r = 0.68, P = 0.03). However, the concentrations of hormones detected in saliva are lower than those in faeces by two orders of magnitude, making it difficult to ensure accuracy. By assessing the applicability of hair, faecal and salivary sampling, we can infer their utility in monitoring the reproductive status and acute and chronic stress levels of giant pandas, thereby providing a means to gauge the success of ongoing habitat restoration efforts and to discuss the feasibility of sample collection from wild populations.

Non-infectious immune complexes downregulate the production of interferons and tumor necrosis factor-α in primary porcine alveolar macrophages in vitro.

Porcine reproductive and respiratory syndrome (PRRS) caused by the PRRS virus (PRRSV) has been harming the pig industry worldwide for nearly 40 years. Although scientific researchers have made substantial efforts to explore PRRSV pathogenesis, the immune factors influencing PRRSV infection still need to be better understood. Infectious virus-antibody immune complexes (ICs) formed by PRRSV and sub-or non-neutralizing antibodies specific for PRRSV may significantly promote the development of PRRS by enhancing PRRSV replication through antibody-dependent enhancement. However, nothing is known about whether PRRSV infection is affected by non-infectious ICs (NICs) formed by non-pathogenic/infectious antigens and corresponding specific antibodies. Here, we found that PRRSV significantly induced the transcripts and proteins of interferon-α (IFN-α), IFN-ß, IFN-γ, IFN-λ1, and tumor necrosis factor-α (TNF-α) in vitro primary porcine alveolar macrophages (PAMs) in the early stage of infection. Our results showed that NICs formed by rabbit-negative IgG (RNI) and pig anti-RNI specific IgG significantly reduced the transcripts and proteins of IFN-α, IFN-ß, IFN-γ, IFN-λ1, and TNF-α in vitro PAMs and significantly elevated the transcripts and proteins of interleukine-10 (IL-10) and transforming growth factor-ß1 (TGF-ß1) in vitro PAMs. NICs-mediated PRRSV infection showed that NICs not only significantly decreased the induction of IFN-α, IFN-ß, IFN-γ, IFN-λ1, and TNF-α by PRRSV but also significantly increased the induction of IL-10 and TGF-ß1 by PRRSV and considerably enhanced PRRSV replication in vitro PAMs. Our data suggested that NICs could downregulate the production of antiviral cytokines (IFN-α/ß/γ/λ1 and TNF-α) during PRRSV infection in vitro and facilitated PRRSV proliferation in its host cells by inhibiting innate antiviral immune response. This study elucidated one novel immune response to PRRSV infection, which would enhance our understanding of the pathogenesis of PRRSV.

Benzimidazole-based structure optimization to discover novel anti-gastric cancer agents targeting ROS/MAPK pathway.

Given the malignancy of gastric cancer, developing highly effective and low-toxic targeted drugs is essential to prolong patient survival and improve patient outcomes. In this study, we conducted structural optimizations based on the benzimidazole scaffold. Notably, compound 8 f presented the most potent antiproliferative activity in MGC803 cells and induced cell cycle arrest at the G0/G1 phase. Further mechanistic studies demonstrated that compound 8 f caused the apoptosis of MGC803 cells by elevating intracellular reactive oxygen species (ROS) levels and activating the mitogen-activated protein kinase (MAPK) signaling pathway, accompanied by corresponding markers change. In vivo investigations additionally validated the inhibitory effect of compound 8 f on tumor growth in xenograft models bearing MGC803 cells without obvious toxicity. Our studies suggest that compound 8 f holds promise as a potential and safe lead compound for developing anti-gastric cancer agents.

Recent research and applications in lipid-based food and lipid-incorporated bioink for 3D printing.

Three-dimensional (3D) printing, as an emerging digital production technology, has recently been receiving increasing attention in food processing. It is important to understand the effect of key ingredients of food materials on the printing, which makes it possible to achieve a wider range of structures using few nozzles and to provide tailored nutrition and personalization. This comprehensive review delves into the latest research on 3D-printed lipid-based foods, encompassing a variety of products such as chocolate, processed cheese, as well as meat. It also explores the development and application of food bioinks that incorporate lipids as a pivotal component, including those based on starch, protein, oleogels, bigels, and emulsions, as well as emulsion gels. Moreover, this review identifies the current challenges and presents an outlook on future research directions in the field of 3D food printing, especially the research and application of lipids in food 3D printing.

Activation of the hypoxia response in the aging cerebrovasculature protects males against cognitive impairment.

Alzheimer's disease (AD) is a neurodegenerative disorder with a distinct sex bias. Age-related vascular alterations, a hallmark of AD onset and progression, are consistently associated with sexual dimorphism. Here, we conducted an integrative meta-analysis of 335,803 single-nucleus transcriptomes and 667 bulk transcriptomes from the vascular system in AD and normal aging to address the underlying sex-dependent vascular aging in AD. All vascular cell types in male AD patients exhibited an activated hypoxia response and downstream signaling pathways including angiogenesis. The female AD vasculature is characterized by increased antigen presentation and decreased angiogenesis. We further confirmed that these sex-biased alterations in the cerebral vascular emerged and were primarily determined in the early stages of AD. Sex-stratified analysis of normal vascular aging revealed that angiogenesis and various stress-response genes were downregulated concurrently with female aging. Conversely, the hypoxia response increased steadily in males upon aging. An investigation of upstream driver transcription factors (TFs) revealed that altered communication between estrogen receptor alpha (ESR1) and hypoxia induced factors during menopause contributes to the inhibition of angiogenesis during normal female vascular aging. Additionally, inhibition of CREB1, a TF that targets estrogen, is also related to female AD. Overall, our study revealed a distinct cerebral vascular profile in females and males, and revealed novel targets for precision medicine therapy for AD.

Comparison between MRI-negative and positive results and the predictors for a poor prognosis in patients with idiopathic acute transverse myelitis.

BACKGROUND: Idiopathic acute transverse myelitis (IATM) is a focal inflammatory disorder of the spinal cord that results in motor, sensory, and autonomic dysfunction. However, the comparative analysis of MRI-negative and MRI-positive in IATM patients were rarely reported. OBJECTIVES: The purpose of this study was to compare MRI-negative with MRI-positive groups in IATM patients, analyze the predictors for a poor prognosis, thus explore the relationship between MRI-negative and prognosis. METHODS: We selected 132 patients with first-attack IATM at the First Affiliated Hospital of Nanchang University from May 2018 to May 2022. Patients were divided into MRI-positive and MRI-negative group according to whether there were responsible spinal MRI lesions, and good prognosis and poor prognosis based on whether the EDSS score ≥ 4 at follow-up. The predictive factors of poor prognosis in IATM patients was analyzed by logistic regression models. RESULTS: Of the 132 patients, 107 first-attack patients who fulfilled the criteria for IATM were included in the study. We showed that 43 (40%) patients had a negative spinal cord MRI, while 27 (25%) patients were identified as having a poor prognosis (EDSS score at follow-up ≥ 4). Compared with MRI-negative patients, the MRI-positive group was more likely to have back/neck pain, spinal cord shock and poor prognosis, and the EDSS score at follow-up was higher. We also identified three risk factors for a poor outcome: absence of second-line therapies, high EDSS score at nadir and a positive MRI result. CONCLUSIONS: Compared with MRI-negative group, MRI-positive patients were more likely to have back/neck pain, spinal cord shock and poor prognosis, with a higher EDSS score at follow-up. The absence of second-line therapies, high EDSS score at nadir, and a positive MRI were risk factors for poor outcomes in patients with first-attack IATM. MRI-negative patients may have better prognosis, an active second-line immunotherapy for IATM patients may improve clinical outcome.

Isolation of camel single domain antibodies against Yersinia pestis V270 antigen based on a semi-synthetic single domain antibody library and development of a VHH-based lateral flow assay.

BACKGROUND: Antibodies have been proven effective as diagnostic agents for detecting zoonotic diseases. The variable domain of camel heavy chain antibody (VHH), as an antibody derivative, may be used as an alternative for traditional antibodies in existing immunodiagnostic reagents for detecting rapidly spreading infectious diseases. OBJECTIVES: To expedite the isolation of specific antibodies for diagnostic purposes, we constructed a semi-synthetic camel single domain antibody library based on the phage display technique platform (PDT) and verified the validity of this study. METHODS: The semi-synthetic single domain antibody sequences consist of two parts: one is the FR1-FR3 region amplified by RT-PCR from healthy camel peripheral blood lymphocytes (PBLs), and the other part is the CDR3-FR4 region synthesised as an oligonucleotide containing CDR3 randomised region. The two parts were fused by overlapping PCR, resulting in the rearranged variable domain of heavy-chain antibodies (VHHs). Y. pestis low-calcium response V protein (LcrV) is an optional biomarker to detect the Y. pestis infection. The semi-synthetic library herein was screened using recombinant (LcrV) as a target antigen. RESULTS: After four cycles of panning the library, four VHH binders targeting 1-270 aa residues of LcrV were isolated. The four VHH genes with unique sequences were recloned into an expression vector and expressed as VHH-hFc chimeric antibodies. The purified antibodies were identified and used to develop a lateral flow immunoassay (LFA) test strip using latex microspheres (LM) for the rapid and visual detection of Y. pestis infection. CONCLUSIONS: These data demonstrate the great potential of the semi-synthetic library for use in isolation of antigen-specific nanobodies and the isolated specific VHHs can be used in antigen-capture immunoassays.

Curcumin Nanocapsules based on carbon dots for photodynamic sterilization towards Listeria monocytogenes and Staphylococcus aureus.

Curcumin (Cur) as a natural food additive and photosensitizer has been widely applied on photodynamic sterilization and preservation for food, but the poor aqueous solubility and light stability restrict its extensive application. In this study, we report a Cur nanocapsules (Cur-CDs) made by carbon dots (CDs). Attributing to the hydrogen bonds formed between Cur and CDs, Cur-CDs exhibits excellent Cur aqueous solubility each to 9286.98 ng/mL (enhanced by 246.27 times) and light stability (enhanced by 1.51 times). The photogenerated electron transmission from Cur to CDs in addition resulted in >1.23 and 1.60 times generation of •O2- and •OH, compared to that of bare Cur. Accordingly, 5.73 × 103 CFU L. monocytogenes, and 5.43 × 103 CFU S. aureus were killed by 0.06 mg/mL Cur-CDs within 20 mins of blue light, showing the promising potential in the development and application of safe and environmentally friendly non-thermal sterilization technology based on Cur-CDs.

A non-invasive osteopontin-targeted phase changeable fluorescent nanoprobe for molecular imaging of myocardial fibrosis.

Due to the elevated fatality rate of cardiovascular diseases, myocardial fibrosis emerges as a prominent pathological alteration in the majority of heart ailments and their associated pathologies, thereby augmenting the likelihood of sudden cardiac death. Consequently, the prompt and obligatory identification of myocardial fibrosis assumes paramount importance in averting malignant incidents among patients afflicted with cardiac disorders. Herein, with higher expression osteopontin (OPN) found in cardiac fibrosis tissue, we have developed a dual-modality imaging probe, namely OPN targeted nanoparticles (OPN@PFP-DiR NPs), which loaded perfluoropentane (PFP) for ultrasound (US) and 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR) for near-infrared fluorescence (NIR) of molecular imaging, to investigate the molecular features of cardiac fibrosis using US and NIR imaging. Subsequently, the OPN@PFP-DiR NPs were administered intravenously to a mouse model of myocardial infarction (MI). The US and NIR molecular imaging techniques were employed to visualize the accumulation of the nanoparticles in the fibrotic myocardium. Hence, this research presents a valuable noninvasive, cost-effective, and real-time imaging method for evaluating cardiac fibrosis, with promising clinical applications.

Concurrently boosted oxygen reduction/evolution electrocatalysis over highly loaded CoNi/onion-like carbon hybrid nanosheets.

Balancing the bicatalytic activities and stabilities between oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is a critical yet challenging task for exploring advanced rechargeable Zinc-air batteries (ZABs). Herein, a hybrid nanosheet catalyst with highly dispersed and densified metallic species is developed to boost the kinetics and stabilities of both ORR and OER concurrently. Through a progressive coordination and pyrolysis approach, we directly prepared highly conductive onion-like carbon (OLC) accommodating dense ORR-active CoNC species and enveloping high-loading OER-active CoNi-synergic structures within a porous lamellar architecture. The resultant CoNi/OLC nanosheet catalyst delivers better ORR and OER activities showcasing a smaller reversible oxygen electrode index (ΔE = Ej10 - E1/2) of 0.71 V, compared to state-of-the-art Pt/C-RuO2 catalysts (0.75 V), Co/amorphous carbon polyhedrons (0.80 V), NiO nanoparticles with higher Ni loading (1.00 V), and most CoNi-based bifunctional catalysts reported so far. The rechargeable ZAB assembled with the developed catalyst achieves a remarkable peak power density of 270.3 mW cm-2 (172 % of that achieved by Pt/C + RuO2) and ultrahigh cycling stability with a negligible increase in voltage gap after 800 h (110 mV increase after 200 h for a Pt/C + RuO2-based battery), standing the top level of those ever reported.

Prinsepia utilis Royle polysaccharides promote skin barrier repair through the Claudin family.

BACKGROUND: Plant polysaccharides have various biological activities. However, few studies have been conducted on the skin barrier of Prinsepia utilis Royle polysaccharide extract (PURP). MATERIALS AND METHODS: The proportions of polysaccharides, monosaccharides and proteins were determined by extracting polysaccharides from fruit meal using water. The healing rate was measured by cell scratch assays. SDS-damaged reconstructed human epidermal models, an acetone-ether-induced mouse model and an IL-4-induced cellular inflammation model were used to detect the effects of polysaccharides on the phenotype, HA, TEWL, and TEER, with further characterizations performed using QRT-PCR, Western blotting, immunofluorescence (IF) assays. RESULTS: PURP contained 35.73% polysaccharides and 11.1% proteins. PURP promoted cell migration and increased skin thickness in a reconstructed human epidermis model. The TEWL significantly decreased, and the HA content significantly increased. PURP significantly increased the TEER and decreased the permeability of the SDS-damaged reconstructed human epidermis model. Claudin-3, Claudin-4, and Claudin-5 were significantly upregulated. IF and Western blot analysis revealed that the Claudin-4 level significantly increased after treatment with PURP. Claudin-1, Claudin-3, Claudin-4, and Claudin-5 gene expression and IF and immunohistochemical staining were significantly increased in mice treated with acetone-ether. PURP promoted the expression of Claudin-1, Claudin-3, Claudin-4, and Claudin-5 after treatment with 100 ng/mL IL-4. PURP also downregulated the expression of NO, IL6, TNFα and NFκB in Raw 264.7 cells and in a mouse model. CONCLUSION: We hypothesize that PURP may repair the skin barrier by promoting the expression of the claudin family and can assist in skin therapy.

Trehalose prevents the formation of aggregates of mutant ataxin-3 and reduces soluble ataxin-3 protein levels in an SCA3 cell model.

Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder caused by mutant ataxin-3 with an abnormally expanded polyQ tract and is the most common dominantly inherited ataxia worldwide. There are no suitable therapeutic options for this disease. Autophagy, a defense mechanism against the toxic effects of aggregation-prone misfolded proteins, has been shown to have beneficial effects on neurodegenerative diseases. Thus, trehalose, which is an autophagy inducer, may have beneficial effects on SCA3. In the present study, we examined the effects of trehalose on an SCA3 cell model. After trehalose treatment, aggregate formation, soluble ataxin-3 protein levels and cell viability were evaluated in HEK293T cells overexpressing ataxin-3-15Q or ataxin-3-77Q. We also explored the mechanism by which trehalose affects autophagy and stress pathways. A filter trap assay showed that trehalose decreased the number of aggregates formed by mutant ataxin-3 containing an expanded polyQ tract. Western blot and Cell Counting Kit-8 (CCK-8) results demonstrated that trehalose also reduced the ataxin-3 protein levels and was safe for ataxin-3-expressing cells, respectively. Western blot and total antioxidant capacity assays suggested that trehalose had great therapeutic potential for treating SCA3, likely through its antioxidant activity. Our data indicate that trehalose plays a neuroprotective role in SCA3 by inhibiting the aggregation and reducing the protein level of ataxin-3, which is also known to protect against oxidative stress. These findings provide a new insight into the possibility of treating SCA3 with trehalose and highlight the importance of inducing autophagy in SCA3.

Propofol Protects the Blood-Brain Barrier After Traumatic Brain Injury by Stabilizing the Extracellular Matrix via Prrx1: From Neuroglioma to Neurotrauma.

The purpose of this study is to explore the shared molecular pathogenesis of traumatic brain injury (TBI) and high-grade glioma and investigate the mechanism of propofol (PF) as a potential protective agent. By analyzing the Chinese glioma genome atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases, we compared the transcriptomic data of high-grade glioma and TBI patients to identify common pathological mechanisms. Through bioinformatics analysis, in vitro experiments and in vivo TBI model, we investigated the regulatory effect of PF on extracellular matrix (ECM)-related genes through Prrx1 under oxidative stress. The impact of PF on BBB integrity under oxidative stress was investigated using a dual-layer BBB model, and we explored the protective effect of PF on tight junction proteins and ECM-related genes in mice after TBI. The study found that high-grade glioma and TBI share ECM instability as an important molecular pathological mechanism. PF stabilizes the ECM and protects the BBB by directly binding to Prrx1 or indirectly regulating Prrx1 through miRNAs. In addition, PF reduces intracellular calcium ions and ROS levels under oxidative stress, thereby preserving BBB integrity. In a TBI mouse model, PF protected BBB integrity through up-regulated tight junction proteins and stabilized the expression of ECM-related genes. Our study reveals the shared molecular pathogenesis between TBI and glioblastoma and demonstrate the potential of PF as a protective agent of BBB. This provides new targets and approaches for the development of novel neurotrauma therapeutic drugs.

Derived from fangchinoline, LYY-35 exhibits an inhibiting effect on human NSCLC cancer A549 cells.

Although fangchinoline has been widely used as an adjunct therapy for a variety of inflammatory and cancerous diseases, its mechanism of action on tumor cells remains unclear. Fangchinoline derivative LYY-35 reduced the number of A549 cells, deformed cell morphology and increased cell debris. Cell viability was significantly reduced, while the same concentration of LYY-35 had little effect on BEAS-2B viability of normal lung epithelial cells. In addition, LYY-35 can also reduce the migration, proliferation and invasion ability of A549 cells. Levels of ß-catenin, ZO-1 and ZEB-1 proteins, biomarkers of cell adhesion and epithelial mesenchymal transformation, were significantly reduced. The levels of superoxide dismutase and lactate dehydrogenase decreased gradually, while the levels of glutathione, malondialdehyde and intracellular and extracellular ROS increased significantly. At the same time, LYY-35 induced increased apoptosis, increased expression of Bax, cleaved caspase3, cleaved PARP1, and decreased expression of Bcl-xl, which blocked the cell cycle to G0/G1 phase. The expressions of cell cycle checkpoint proteins Cyclin B1, Cyclin E1, CDK6, PCNA and PICH were significantly decreased. With the increase of LYY-35 concentration, the trailing phenomenon was more obvious in single cell gel electrophoresis. DNA damage repair proteins: BLM, BRCA-1 and PARP-1 expression decreased gradually.LYY-35 can inhibit the proliferation of non-small cell lung cancer A549 cells, block cell cycle, promote apoptosis, increase ROS production, cause DNA damage and interfere with DNA replication. LYY-35 is promising for the treatment of non-small cell lung cancer in the future.

Decoding heterogeneous and coordinated tissue architecture in glioblastoma using spatial transcriptomics.

Glioblastoma multiforme (GBM) is one of the most lethal brain tumors, characterized by profound heterogeneity. While single-cell transcriptomic studies have revealed extensive intra-tumor heterogeneity, shed light on intra-tumor diversity, spatial intricacies remain largely unexplored. Leveraging clinical GBM specimens, this study employs spatial transcriptomics technology to delve into gene expression heterogeneity. Our investigation unveils a significant enrichment of tissue stem cell signature in regions bordering necrosis and the peritumoral area, positively correlated with the mesenchymal subtype signature. Moreover, upregulated genes in these regions are linked with extracellular matrix (ECM)-receptor interaction, proteoglycans, as well as vascular endothelial growth factor (VEGF) and angiopoietin-Tie (ANGPT) signaling pathways. In contrast, signatures related to glycogen metabolism and oxidative phosphorylation show no relevance to pathological zoning, whereas creatine metabolism signature is notably exclusive to vascular-enriched areas. These spatial profiles not only offer valuable references but also pave the way for future in-depth functional and mechanistic investigations into GBM progression.

Effects of different plasma treatments on bonding properties of zirconia.

This in vitro study was to evaluate the effect of different non-thermal atmospheric pressure plasma (NTP) on shear bond strength (SBS) between yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) and self-adhesive resin cement. In this study, The Y-TZP specimens were divided into 4 groups according to the surface treatment methods as follows: Control (no surface treatment), Sb (Sandblasting), AP(argon NTP), and CP(20 % oxygen and 80 % argon combination NTP). Y-TZP specimens were randomly selected from each group to observe and test the following indexes: scanning electron microscope to observe the surface morphology; atomic force microscope to detect the surface roughness; contact angle detector to detect the surface contact angle; energy spectrometer to analyze the surface elements. Then, resin cement (Rely X-U200) was bonded to human isolated teeth with Y-TZP specimens to measure SBS. The results showed that for the SE test, the NTP group was significantly higher than the control group (p < 0.05). The results of the SBS test showed that the SBS values of the NTP group were significantly higher than those of the other groups, regardless of the plasma treatment (p < 0.05). However, there was no significant difference between groups AP and CP in a test of SBS (p > 0.05). This study shows that non-thermal atmospheric pressure plasma can improve the shear bond strength of Y-TZP by increasing the surface energy. The addition of oxygen ratio to argon is more favorable to increase the shear bond strength and is worth further investigation.

Split Luciferase Molecular Tension Sensors for Bioluminescent Readout of Mechanical Forces in Biological Systems.

The ability of proteins to sense and transmit mechanical forces underlies many biological processes, but characterizing these forces in biological systems remains a challenge. Existing genetically encoded force sensors typically rely on fluorescence or bioluminescence resonance energy transfer (FRET or BRET) to visualize tension. However, these force sensing modules are relatively large, and interpreting measurements requires specialized image analysis and careful control experiments. Here, we report a compact molecular tension sensor that generates a bioluminescent signal in response to tension. This sensor (termed PILATeS) makes use of the split NanoLuc luciferase and consists of the H. sapiens titin I10 domain with the insertion of a 10-15 amino acid tag derived from the C-terminal ß-strand of NanoLuc. Mechanical load across PILATeS mediates exposure of this tag to recruit the complementary split NanoLuc fragment, resulting in force-dependent bioluminescence. We demonstrate the ability of PILATeS to report biologically meaningful forces by visualizing forces at the interface between integrins and extracellular matrix substrates. We further use PILATeS as a genetically encoded sensor of tension experienced by the mechanosensing protein vinculin. We anticipate that PILATeS will provide an accessible means of visualizing molecular-scale forces in biological systems.

Effect of airflow rate on droplet deposition of an impinging-jet inhaler in the human respiratory tract.

This paper presents a numerical investigation to understand the transport and deposition of sprays emitted by an impinging-jet inhaler in the human respiratory tract under different inhalation flow rates. An injection model is used for the numerical simulations considering the spreading angles of the spray in the two directions, which are measured from experiments. The model parameter is adjusted to match the mean droplet size measured in the previous experiment. A time-varying sinusoidal inhalation flow rate is utilized as airflow conditions, which is closer to the actual situation when using an inhaler. The results demonstrate that the inhalation airflow rate significantly affects the spray's transport behavior and deposition results in the respiratory tract. Both excessively high and low inhalation flow rates lead to an increase in deposition in the mouth-throat. A moderate inhalation flow rate reduces throat deposition while maximizing lung deposition. Higher inhalation flow rates enable faster delivery of the droplets to the lungs, whereas lower inhalation flow rates achieve a more uniform deposition over time in the lungs. The amount of deposition in different parts of the lung lobes follows a fixed order. This study provides valuable insights for optimizing the inhalation flow rate conditions of the impinging-jet inhaler for clinical applications.

Lattice Matching and Microstructure of the Aromatic Amide Fatty Acid Salts Nucleating Agent on the Crystallization Behavior of Recycled Polyethylene Terephthalate.

To solve the decrease in the crystallization, mechanical and thermal properties of recycled polyethylene terephthalate (rPET) during mechanical recycling, the aromatic amide fatty acid salt nucleating agents Na-4-ClBeAmBe, Na-4-ClBeAmGl and Na-4-ClAcAmBe were synthesized and the rPET/nucleating agent blend was prepared by melting blending. The molecular structure, the thermal stability, the microstructure and the crystal structure of the nucleating agent were characterized in detail. The differential scanning calorimetry (DSC) result indicated that the addition of the nucleating agent improved the crystallization temperature and accelerated the crystallization rate of the rPET. The nucleation efficiencies (NE) of the Na-4-ClBeAmBe, Na-4-ClBeAmGl and Na-4-ClAcAmBe were increased by 87.2%, 87.3% and 41.7% compared with rPET which indicated that Na-4-ClBeAmBe and Na-4-ClBeAmGl, with their long-strip microstructures, were more conducive to promoting the nucleation of rPET. The equilibrium melting points (Tm0) of rPET/Na-4-ClBeAmBe, rPET/Na-4-ClBeAmGl and rPET/Na-4-ClAcAmBe were increased by 11.7 °C, 18.6 °C and 1.9 °C compared with rPET, which illustrated that the lower mismatch rate between rPET and Na-4-ClBeAmGl (0.8% in b-axis) caused Na-4-ClBeAmGl to be the most capable in inducing the epitaxial crystallization and orient growth along the b-axis direction of the rPET. The small angle X-ray diffraction (SAXS) result proved this conclusion. Meanwhile, the addition of Na-4-ClBeAmGl caused the clearest increase in the rPET of its flexural strength and heat-distortion temperature (HDT) at 20.4% and 46.7%.

A polymeric 1H/19F dual-modal MRI contrast agent with a snowman-like Janus nanostructure.

Magnetic resonance imaging (MRI) has emerged as a pivotal tool in contemporary medical diagnostics, offering non-invasive and high-resolution visualization of internal structures. Contrast agents are essential for enhancing MRI resolution, accurate lesion detection, and early pathology identification. While gadolinium-based contrast agents are widely used in clinics, safety concerns have prompted exploration of metal-free alternatives, including fluorine and nitroxide radical-based MRI contrast agents. Fluorine-containing compounds exhibit excellent MRI capabilities, with 19F MRI providing enhanced resolution and quantitative assessment. Nitroxide radicals, such as PROXYL and TEMPO, offer paramagnetic properties for MRI contrast. Despite their versatility, nitroxide radicals suffer from lower relaxivity values (r1) compared to gadolinium. Dual-modal imaging, combining 1H and 19F MRI, has gained prominence for its comprehensive insights into biological processes and disease states. However, existing dual-modal agents predominantly utilize gadolinium-organic ligands without incorporating nitroxide radicals. Here, we introduce a novel dual-modal MRI contrast agent (J-CA) featuring a Janus asymmetric nanostructure synthesized via seeded emulsion polymerization and post-modification. J-CA demonstrates excellent in vitro and in vivo performance in both 19F and 1H MRI, with a T2 relaxation time of 5 ms and an r1 value of 0.31 mM-1 s-1, ensuring dual-modal imaging capability. Moreover, J-CA exhibits superior biocompatibility and organ targeting, making it a promising candidate for precise lesion imaging and disease diagnosis. This work introduces a new avenue for metal-free dual-modal MRI, addressing safety concerns associated with traditional contrast agents.