A novel quantitative method to evaluate lumbar disc degeneration: MRI histogram analysis.

PURPOSE: This study aimed to use MRI histogram analysis to routine MRI sequences to evaluate lumbar disc degeneration (LDD), illustrate the correlation between this novel method and the traditional Pfirrmann classification method, and more importantly, perform comprehensive agreement analysis of MRI histogram analysis in various situations to evaluate its objectivity and stability. METHODS: Lumbar MRI images from 133 subjects were included in this study. LDD was classified into grades by Pfirrmann classification and was measured as peak separation value by MRI histogram analysis. Correlation analysis between the two methods was performed and cutoff values were determined. In addition, the agreement analysis of peak separation value was performed by intraclass correlation coefficient (ICC) in four scenarios, including inter-resolution, inter-observer, inter-regions of interest (ROI) and inter-slice. RESULTS: Peak separation values were strongly correlated with Pfirrmann grades (r = - 0.847). The inter-resolution agreements of peak separation value between original image resolution of 2304 × 2304 and compressed image resolutions (1152 × 1152, 576 × 576, 288 × 288) were good to excellent (ICCs were 0.916, 0.876 and 0.822), except 144 × 144 was moderate (ICC = 533). The agreements of inter-observer (ICC = 0.982) and inter-ROI (ICC = 0.915) were excellent. Compared with the mid-sagittal slice, the inter-slice agreements were good for the first adjacent slices (ICCs were 0.826 and 0.844), and moderate to good for the second adjacent slices (ICC = 0.733 and 0.753). CONCLUSION: MRI histogram analysis, used in routine MRI sequences, demonstrated a strong correlation with Pfirrmann classification and good agreements in various scenarios, expanding the range of application and providing an effective, objective and quantitative tool to evaluate LDD.

Transcranial Ultrasound Stimulation Improves Memory Performance of Parkinsonian Mice.

Cognitive impairment is one of the most common non-motor symptoms of Parkinson's disease (PD). Previous studies have demonstrated that low-intensity transcranial ultrasound stimulation can significantly suppress the motor symptoms of PD. However, whether ultrasound stimulation can improve cognitive ability in PD and the related neural oscillation mechanism remain unclear to date. To evaluate the effect of ultrasound stimulation on memory ability in PD and explore its neural oscillation mechanism. Ultrasonography was used for 7-day stimulation of the CA1 in transgenic mice with PD. The working memory ability of the PD mice was then tested using novel object discrimination, and the local field potential and spikes in the mice CA1 were recorded at the same time as in the behavioral test. We found that ultrasound stimulation of the PD mice CA1 for 4 days: 1) significantly increased their learning and memory ability, although the learning and memory ability on the 7th day after the stimulation stopped was not significantly different from that before stimulation (P>0.05); 2) significantly increased the relative power of theta, low gamma, and high gamma frequency bands of the local field potential, and the phase amplitude coupling strength between theta and low gamma and between theta and high gamma; and 3) modulated the phase-locking angle between the spike of interneuron and theta wave to a 180°-360° rise cycle. Transcranial ultrasound stimulation can improve the learning and memory abilities of PD mice, and evoking neural oscillations in the CA1 is the potential mechanism.

Evaluation of the effectiveness of using prednisolone, tacrolimus, and intravenous immunoglobulin combination therapy on immune-mediated necrotizing myopathy-A non-randomized, observational research.

OBJECTIVE: To recruit immune-mediated necrotizing myopathy (IMNM) patients with extramuscular manifestations who were refractory to initial therapy with either monotherapy with prednisolone or dual therapy with prednisolone and immunosuppressants. These patients subsequently received a combination of prednisolone, tacrolimus, and intravenous immunoglobulin (IVIG), and the efficacy of this treatment regimen was assessed in patients with IMNM. METHOD: ①Clinical data and treatment measures are as follows: This study enrolled IMNM patients who were treated at the Neurology Department of the First Medical Center of PLA General Hospital from April 2020 to May 2023. These patients received a combination therapy of prednisolone, tacrolimus, and IVIG. ②Observational indicators included manual muscle test for 8 groups of muscles (MMT-8), muscle enzyme levels (creatine kinase (CK), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST)), and myositis disease activity assessment tool (MDAAT). RESULTS: This study enrolled eight patients. All observational indicators declined after treatment compared to before treatment, and these changes were statistically significant. Moreover, extramuscular manifestations also ameliorated compared to before treatment. CONCLUSION: The combination therapy of prednisolone, tacrolimus, and IVIG has demonstrated favorable efficacy in IMNM and broadened the treatment options for this disease. However, the results still require further validation by large-scale and randomized controlled studies.

Cellular Uptake and Transport Mechanism Investigations of PEGylated Niosomes for Improving the Oral Delivery of Thymopentin.

BACKGROUND: Although its immunomodulatory properties make thymopentin (TP5) appealing, its rapid metabolism and inactivation in the digestive system pose significant challenges for global scientists. PEGylated niosomal nanocarriers are hypothesized to improve the physicochemical stability of TP5, and to enhance its intestinal permeability for oral administration. METHODS: TP5-loaded PEGylated niosomes were fabricated using the thin film hydration method. Co-cultured Caco-2 and HT29 cells with different ratios were screened as in vitro intestinal models. The cytotoxicity of TP5 and its formulations were evaluated using an MTT assay. The cellular uptake and transport studies were investigated in the absence or presence of variable inhibitors or enhancers, and their mechanisms were explored. RESULTS AND DISCUSSION: All TP5 solutions and their niosomal formulations were nontoxic to Caco-2 and HT-29 cells. The uptake of TP5-PEG-niosomes by cells relied on active endocytosis, exhibiting dependence on time, energy, and concentration, which has the potential to significantly enhance its cellular uptake compared to TP5 in solution. Nevertheless, cellular transport rates were similar between TP5 in solution and its niosomal groups. The cellular transport of TP5 in solution was carried out mainly through MRP5 endocytosis and a passive pathway and effluxed by MRP5 transporters, while that of TP5-niosomes and TP5-PEG-niosomes was carried out through adsorptive- and clathrin-mediated endocytosis requiring energy. The permeability and transport rate was further enhanced when EDTA and sodium taurocholate were used as the penetration enhancers. CONCLUSIONS: This research has illustrated that PEG-niosomes were able to enhance the cellular uptake and maintain the cellular transport of TP5. This study also shows this formulation's potential to serve as an effective carrier for improving the oral delivery of peptides.

Production optimization of food functional factor ergothioneine in wild-type red yeast Rhodotorula mucilaginosa DL-X01.

BACKGROUND: Ergothioneine (EGT) is a high-value food functional factor that cannot be synthesized by humans and other vertebrates, and the low yield limits its application. RESULTS: In this study, the optimal fermentation temperature, fermentation time, initial pH, inoculum age, and inoculation ratio on EGT biosynthesis of Rhodotorula mucilaginosa DL-X01 were optimized. In addition, the effects of three key precursor substances - histidine, methionine, and cysteine - on fungal EGT synthesis were verified. The optimal conditions were further obtained by response surface optimization. The EGT yield of R. mucilaginosa DL-X01 under optimal fermentation conditions reached 64.48 ± 2.30 mg L-1 at shake flask fermentation level. Finally, the yield was increased to 339.08 ± 3.31 mg L-1 (intracellular) by fed-batch fermentation in a 5 L bioreactor. CONCLUSION: To the best of our knowledge, this is the highest EGT yield ever reported in non-recombinant strains. The fermentation strategy described in this study will promote the efficient biosynthesis of EGT in red yeast and its sustainable production in the food industry. © 2024 Society of Chemical Industry.

Pulmonary artery anastomosis during lung transplantation: a novel technique.

Pulmonary artery anastomosis (PAA) is a critical step in lung transplantation. The conventional approach involves end-to-end anastomosis, which can lead to arterial tortuosity, oozing, stenosis, and thrombosis. Here, we present a modified PAA technique for lung transplantation. The anesthesia protocol and the incision for lung transplantation adhere to standard lung transplantation protocols. The primary innovation is the enhanced pulmonary anastomosis technique. The donor and recipient artery stumps are adjusted to restore their natural anatomical alignment. The donor-recipient stump is everted, ensuring precise alignment of the intima of the donor and recipient arteries. Both ends of the anastomosis are secured using 5-0 Prolene sutures to ensure stability and traction, followed by continuous suturing. In this study, seven patients underwent PAA using this novel technique. Notably, no bleeding was observed upon unveiling and deaerating the anastomosis, eliminating the need for additional sutures. Furthermore, no pulmonary artery torsion or significant prolongation of the anastomotic procedure was observed. Postoperative computed tomography of the chest revealed no anastomotic stenosis or mural thrombosis. This novel cuff anastomosis technique can reduce the risk of thrombosis and prevent torsion and stenosis in the reconstructed artery.

Combination of mangiferin and T0901317 targeting autophagy promotes cholesterol efflux from macrophage foam cell in atherosclerosis.

BACKGROUND: The synthetic liver X receptor ligand (LXR) T0901317 (T0) has been reported to attenuate atherosclerosis (AS) without hyperglyceridemia due to innovative drug combination or nano-sized drug delivery. Given the key roles of mangiferin (MGF) in lipid metabolism and atherogenesis, it is critical to investigate progression of atherosclerotic lesion after combined treatment of MGF and T0. METHODS: Atherosclerotic plaque formation and hepatic lipid accumulation were compared in Apoe-/- mice among T0 and/or MGF treatment. The in vitro functions of MGF and T0 were analyzed by Oil-red O staining, cholesterol efflux assay, transmission electron microscopy and western blot analyses with or without acetylated low density lipoprotein. RESULTS: The combination therapy are effective regulators for atherosclerotic plaque formation in Apoe-/- mice, due to upregulation of ABCA1 and ABCG1 induced by LXR activation. Subsequently, we identified autophagy promoted by MGF and T0 treatment establishes a positive feedback loop that increases cholesterol efflux, resulted from LXRα activation. Under atherogenic conditions, the autophagy inhibitor CQ abolished the enhancement effect on cholesterol outflow of MGF and T0. Mechanically, MGF and T0 promotes LXRα and mTOR/AMPK signaling cascade in macrophage, and promotes AMPK signaling cascade in hepatocyte, leading to lipid metabolic homeostasis. CONCLUSIONS: Altogether, our findings reveal that MGF and T0 engages in AS therapy without side effects by activating AMPK-dependent autophagy to promote macrophage cholesterol efflux, and MGF might serve as a natural compound to assist T0 in AS via targeting autophagy.

Global environmental and toxicological impacts of polybrominated diphenyl ethers versus organophosphate esters: A comparative analysis and regrettable substitution dilemma.

The prevalence of organophosphate esters (OPEs) in the global environment is increasing, which aligns with the decline in the usage of polybrominated diphenyl ethers (PBDEs). PBDEs, a category of flame retardants, were banned and classified as persistent organic pollutants (POPs) through the Stockholm Convention due to their toxic and persistent properties. Despite a lack of comprehensive understanding of their ecological and health consequences, OPEs were adopted as replacements for PBDEs. This research aims to offer a comparative assessment of PBDEs and OPEs in various domains, specifically focusing on their persistence, bioaccumulation, and toxicity (PBT) properties. This study explored physicochemical properties (such as molecular weight, octanol-water partition coefficient, octanol-air partition coefficient, Henry's law constant, and vapor pressures), environmental behaviors, global concentrations in environmental matrices (air, water, and soil), toxicities, bioaccumulation, and trophic transfer mechanisms of both groups of compounds. Based on the comparison and analysis of environmental and toxicological data, we evaluate whether OPEs represent another instance of regrettable substitution and global contamination as much as PBDEs. Our findings indicate that the physical and chemical characteristics, environmental behaviors, and global concentrations of PBDEs and OPEs, are similar and overlap in many instances. Notably, OPE concentrations have even surged by orders of several magnitude compared to PBDEs in certain pristine regions like the Arctic and Antarctic, implying long-range transport. In many instances, air and water concentrations of OPEs have been increased than PBDEs. While the bioaccumulation factors (BAFs) of PBDEs (ranging from 4.8 to 7.5) are slightly elevated compared to OPEs (-0.5 to 5.36) in aquatic environments, both groups of compounds exhibit BAF values beyond the threshold of 5000 L/kg (log10 BAF > 3.7). Similarly, the trophic magnification factors (TMFs) for PBDEs (ranging from 0.39 to 4.44) slightly surpass those for OPEs (ranging from 1.06 to 3.5) in all cases. Metabolic biotransformation rates (LogKM) and hydrophobicity are potentially major factors deciding their trophic magnification potential. However, many compounds of PBDEs and OPEs show TMF values higher than 1, indicating biomagnification potential. Collectively, all data suggest that PBDEs and OPEs have the potential to bioaccumulate and transfer through the food chain. OPEs and PBDEs present a myriad of toxicity endpoints, with notable overlaps encompassing reproductive issues, oxidative stress, developmental defects, liver dysfunction, DNA damage, neurological toxicity, reproductive anomalies, carcinogenic effects, and behavior changes. Based on our investigation and comparative analysis, we conclude that substituting PBDEs with OPEs is regrettable based on PBT properties, underscoring the urgency for policy reforms and effective management strategies. Addressing this predicament before an exacerbation of global contamination is imperative.

Transcranial ultrasound stimulation selectively affects cortical neurovascular coupling across neuronal types and LFP frequency bands.

Previous studies have affirmed that transcranial ultrasound stimulation (TUS) can influence cortical neurovascular coupling across low-frequency (0-2 Hz)/high-frequency (160-200 Hz) neural oscillations and hemodynamics. Nevertheless, the selectivity of this coupling triggered by transcranial ultrasound stimulation for spike activity (> 300 Hz) and additional frequency bands (4-150 Hz) remains elusive. We applied transcranial ultrasound stimulation to mice visual cortex while simultaneously recording total hemoglobin concentration, spike activity, and local field potentials. Our findings include (1) a significant increase in coupling strength between spike firing rates of putative inhibitory neurons/putative excitatory neurons and total hemoglobin concentration post-transcranial ultrasound stimulation; (2) an ~ 2.1-fold higher Pearson correlation coefficient between putative inhibitory neurons and total hemoglobin concentration compared with putative excitatory neurons and total hemoglobin concentration (*P < 0.05); (3) a notably greater cross-correlation between putative inhibitory neurons and total hemoglobin concentration than that between putative excitatory neurons and total hemoglobin concentration (*P < 0.05); (4) an enhancement of Pearson correlation coefficient between the relative power of γ frequency band (30-80 Hz), hγ frequency band (80-150 Hz) and total hemoglobin concentration following transcranial ultrasound stimulation (*P < 0.05); and (5) strongest cross-correlation observed at negative delay for θ frequency band, and positive delay for α, ß, γ, hγ frequency bands. Collectively, these results demonstrate that cortical neurovascular coupling evoked by transcranial ultrasound stimulation exhibits selectivity concerning neuronal types and local field potential frequency bands.

Anemoside B4 ameliorates dextran sulfate sodium (DSS)-induced colitis through inhibiting NLRP3 inflammasome and modulating gut microbiota.

Ulcerative colitis (UC) has been recognized as a chronic and relapsing inflammatory disease of the gastrointestinal tract. Clinically, aminosalicylates, immunosuppressants and biological agents are commonly used to treat UC at different stages of the disease. However, these drugs often have side effects. Here, we investigated the anti-UC activity of Anemoside B4 (AB4) in mice with dextran sulfate sodium (DSS) induced colitis. Colon tissues, serum, and colonic contents were collected for assessment of intestinal barrier function, inflammatory cytokines production and microenvironment of intestinal microbiota. Results showed that AB4 alleviated colon shortening, weight lossing and histopathological damage in DSS-induced mice. In addition, we demonstrated both in vivo and in vitro that AB4 remarkably ameliorated colonic inflammation through suppressing NLRP3 pathway. Moreover, AB4 strengthened the intestinal epithelial barrier by regulating myosin light chain kinase (MLCK)-phosphorylated myosin light chain 2 (pMLC2) signaling pathway. Furthermore, we performed 16 S rRNA gene sequencing and fecal microbiome transplantation (FMT) experiments to demonstrate that AB4 alleviated colitis through regulating dysbiosis of intestinal microbiota. These results revealed that AB4 effectively ameliorate experimental UC mainly through regulating MLCK/pMLC2 pathway, NLRP3 pathway and dysbiosis of microbiota, provided new insights into the development of novel anti-UC drugs.

A stretchable hardness sensor for the assessment of skin disease in systemic sclerosis.

OBJECTIVE: To determine the validity of a hardness sensor to objectively assess skin induration in patients with systemic sclerosis, and to compare the hardness sensor with the modified Rodnan skin score (MRSS) and a durometer. METHODS: The skin induration was measured in two assessments: a Latin square experiment to examine the hardness sensor's intraobserver and interobserver reliability; and a longitudinal cohort to evaluate the distribution of hardness sensor measurements, the correlation between hardness sensor, durometer and MRSS, and the sensitivity to change in skin hardness. Other outcome data collected included the health assessment questionnaire (HAQ) disability index and Keitel function test (KTF) score. RESULTS: The reliability of the hardness sensor was excellent, with high intraobserver and interobserver intraclass correlation coefficients (0.97; 0.96), which was higher than MRSS (0.86; 0.74). Interobserver reproducibility of hardness sensor was only poor in abdomen (0.38), yet for durometer it was poor in face (0.11) and abdomen (0.33). The hardness sensor score provided a greater dynamic evaluation range than MRSS. Total hardness sensor score correlated well with MRSS (r=0.90, p<0.001), total durometer score (r=0.95, p<0.001), HAQ disability index (r=0.70, p<0.001) and KTF score (r=0.66, p<0.001). Change in hardness sensor score also correlated with change in MRSS (r=0.78, p<0.001), total durometer score (r=0.85, p<0.001), HAQ disability index (r=0.76, p<0.001) and KTF score (r=0.67, p<0.001). CONCLUSION: The hardness sensor showed greater reproducibility and accuracy than MRSS, and more application sites than durometer; it can also reflect patients' self-assessments and function test outcomes.

YTHDC1 as a tumor progression suppressor through modulating FSP1-dependent ferroptosis suppression in lung cancer.

Ferroptosis is a regulated cell death process initiated by iron-dependent phospholipid peroxidation and is mainly suppressed by GPX4-dependent and FSP1-dependent surveillance mechanisms. However, how the ferroptosis surveillance system is regulated during cancer development remains largely unknown. Here, we report that the YTHDC1-mediated m6A epigenetic regulation of FSP1 alleviates the FSP1-dependent ferroptosis suppression that partially contributes to the tumor suppressive role of YTHDC1 in lung cancer progression. YTHDC1 knockdown promoted the lung tumor progression and upregulated FSP1 protein level that resulted in ferroptosis resistance of lung cancer cells. Silencing FSP1 abrogated YTHDC1 knockdown-induced proliferation increase and ferroptosis resistance. Mechanistically, YTHDC1 binding to the m6A sites in the FSP1 3'-UTR recruited the alternative polyadenylation regulator CSTF3 to generate a less stable shorter 3'-UTR contained FSP1 mRNA, whereas YTHDC1 downregulation generated the longer 3'-UTR contained FSP1 mRNA that is stabilized by RNA binding protein HuR and thus led to the enhanced FSP1 protein level. Therefore, our findings identify YTHDC1 as a tumor progression suppressor in lung cancer and a ferroptosis regulator through modulating the FSP1 mRNA stability and thus suggest a ferroptosis-related therapeutic option for YTHDC1high lung cancer.

Discovery of Novel Fedratinib-Based HDAC/JAK/BRD4 Triple Inhibitors with Remarkable Antitumor Activity against Triple Negative Breast Cancer.

Multitarget HDAC inhibitors capable of simultaneously blocking the BRD4-LIFR-JAK1-STAT3 signaling pathway hold great potential for the treatment of TNBC and other solid tumors. Herein, novel Fedratinib-based multitarget HDAC inhibitors were rationally designed, synthesized, and biologically evaluated, among which compound 25ap stood out as a potent HDAC/JAK/BRD4 triple inhibitor. Satisfyingly, compound 25ap led to concurrent inhibition of HDACs and the BRD4-LIFR-JAK1-STAT3 signaling pathway, which was validated by hyper-acetylation of histone and α-tubulin, hypo-phosphorylation of STAT3, downregulation of LIFR, MCL-1, and c-Myc in MDA-MB-231 cells. The multitarget effects of 25ap contributed to its robust antitumor response, including potent antiproliferative activity, remarkable apoptosis-inducing activity, and inhibition of colony formation. Notably, 25ap possessed an acceptable therapeutic window between normal and cancerous cells, desirable in vitro metabolic stability in mouse microsome, and sufficient in vivo exposure via intraperitoneal administration. Additionally, the in vivo antitumor potency of 25ap was demonstrated in an MDA-MB-231 xenograft model.

Microplastics in the Taiwan Strait and adjacent sea: Spatial variations and lateral transport.

This study investigates the distribution, structural properties, and potential impacts of oceanic processes on microplastics (MPs) in the Taiwan Strait (TWS) and surrounding seas. With an average of 174 particles/m3, the MP abundance in surface seawater ranged from 84 to 389 particles/m3. MP abundance ranged from 16 to 382 particles/kg in sediments, with a median of 121 particles/kg. Fragment and fiber were the two most frequently detected shapes. These MPs were found to be composed primarily of carbon and oxygen elements at 70-90% levels using energy-dispersive X-ray spectroscopy. Additionally, several examples had trace levels of metallic components. Black was the color that MPs saw the most often out of all the hues. The two main types of polymers are polyester and rayon, and their production is influenced by home sewage discharge and synthetic fiber production. The main routes of MP transport were land source input, riverine input, and oceanic currents. This study showed that salinity affects the distribution of MPs, with high-salinity seawater serving to saturate their presence. On the other hand, upwelling raises MP concentrations by bringing nutrients from the deep to the surface. Furthermore, it has been discovered that the dilution of the Pearl River plume increases the MP prevalence in the region. The South China Sea Warm Current had the highest lateral MPs transport flux (2.1 × 1014 particles/y), which was followed by the Taiwan Strait Current area (1.0 × 1014 particles/y) and the Guangdong coastal areas (8.6 × 1013 particles/y). In sediments, the MP prevalence was inversely correlated with particle size. Flocculation processes probably made it easier for MPs to travel down the water column and deposit themselves on the aquatic substrate. Although the relationship between MPs, total organic carbon, and total organic nitrogen was not correlated, a favorable trend showed that MPs may discreetly contribute to carbon storage in coastal sediment.

Corrigendum: Characteristics of cardiac involvement in immune-mediated necrotizing myopathy.

[This corrects the article DOI: 10.3389/fimmu.2023.1094611.].

SVCNet: Scribble-Based Video Colorization Network With Temporal Aggregation.

In this paper, we propose a scribble-based video colorization network with temporal aggregation called SVCNet. It can colorize monochrome videos based on different user-given color scribbles. It addresses three common issues in the scribble-based video colorization area: colorization vividness, temporal consistency, and color bleeding. To improve the colorization quality and strengthen the temporal consistency, we adopt two sequential sub-networks in SVCNet for precise colorization and temporal smoothing, respectively. The first stage includes a pyramid feature encoder to incorporate color scribbles with a grayscale frame, and a semantic feature encoder to extract semantics. The second stage finetunes the output from the first stage by aggregating the information of neighboring colorized frames (as short-range connections) and the first colorized frame (as a long-range connection). To alleviate the color bleeding artifacts, we learn video colorization and segmentation simultaneously. Furthermore, we set the majority of operations on a fixed small image resolution and use a Super-resolution Module at the tail of SVCNet to recover original sizes. It allows the SVCNet to fit different image resolutions at the inference. Finally, we evaluate the proposed SVCNet on DAVIS and Videvo benchmarks. The experimental results demonstrate that SVCNet produces both higher-quality and more temporally consistent videos than other well-known video colorization approaches. The codes and models can be found at https://github.com/zhaoyuzhi/SVCNet.

Enhanced Cellular Uptake and Transport of Bovine Lactoferrin Using Pectin- and Chitosan-Modified Solid Lipid Nanoparticles.

AIM: The aim of this project is to use pectin- and chitosan-modified solid lipid nanoparticles for bovine lactoferrin to enhance its cellular uptake and transport. METHODS: Solid lipid particles containing bovine lactoferrin (bLf) were formulated through the solvent evaporation technique, incorporating stearic acid along with either chitosan or pectin modification. bLf cellular uptake and transport were evaluated in vitro using the human adenocarcinoma cell line Caco-2 cell model. RESULTS AND DISCUSSION: The bLf-loaded SLPs showed no significant effect on cytotoxicity and did not induce apoptosis within the eight-hour investigation. The use of confocal laser scanning microscopy confirmed that bLf follows the receptor-mediated endocytosis, whereas the primary mechanism for the cellular uptake of SLPs was endocytosis. The bLf-loaded SLPs had significantly more cellular uptake compared to bLf alone, and it was observed that this impact varied based on the time, temperature, and concentration. Verapamil and EDTA were determined to raise the apparent permeability coefficients (App) of bLf and bLf-loaded SLPs. CONCLUSION: This occurred because they hindered efflux by interacting with P-glycoproteins and had a penetration-enhancing influence. These findings propose the possibility of an additional absorption mechanism for SLPs, potentially involving active transportation facilitated by the P-glycoprotein transporter in Caco-2 cells. These results suggest that SLPs have the potential to be applied as effective carriers to improve the oral bioavailability of proteins and peptides.

Ocean Stratification Impacts on Dissolved Polycyclic Aromatic Hydrocarbons (PAHs): From Global Observation to Deep Learning.

Ocean stratification plays a crucial role in many biogeochemical processes of dissolved matter, but our understanding of its impact on widespread organic pollutants, such as polycyclic aromatic hydrocarbons (PAHs), remains limited. By analyzing dissolved PAHs collected from global oceans and marginal seas, we found different patterns in vertical distributions of PAHs in relation to ocean primary productivity and stratification index. Notably, a significant positive logarithmic relationship (R2 = 0.50, p < 0.05) was observed between the stratification index and the PAH stock. To further investigate the impact of ocean stratification on PAHs, we developed a deep learning neural network model. This model incorporated input variables determining the state of the seawater or the stock of PAHs. The modeled PAH stocks displayed substantial agreement with the observed values (R2 ≥ 0.92), suggesting that intensified stratification could prompt the accumulation of PAHs in the water column. Given the amplified effect of global warming, it is imperative to give more attention to increased ocean stratification and its impact on the environmental fate of organic pollutants.