Revitalizing gut barrier integrity: miR-192-5p's role in enhancing autophagy via Rictor in enteritis.

BACKGROUND: Intestinal inflammation and compromised barrier function are critical factors in the pathogenesis of gastrointestinal disorders. This study aimed to investigate the role of miR-192-5p in modulating intestinal epithelial barrier (IEB) integrity and its association with autophagy. METHODS: A DSS-induced colitis model was used to assess the effects of miR-192-5p on intestinal inflammation. In vitro experiments involved cell culture and transient transfection techniques. Various assays, including dual-luciferase reporter gene assays, quantitative real-time PCR, western blotting, and measurements of transepithelial electrical resistance, were performed to evaluate changes in miR-192-5p expression, Rictor levels, and autophagy flux. Immunofluorescence staining, H&E staining, TEER measurements, and FITC-dextran analysis were also employed. RESULTS: Our findings revealed a reduced expression of miR-192-5p in inflamed intestinal tissues, correlating with impaired IEB function. Overexpression of miR-192-5p alleviated TNF-induced IEB dysfunction by targeting Rictor, resulting in enhanced autophagy flux in enterocytes (ECs). Moreover, the therapeutic potential of miR-192-5p was substantiated in colitis mice, wherein increased miR-192-5p expression ameliorated intestinal inflammatory injury by enhancing autophagy flux in ECs through the modulation of Rictor. CONCLUSION: Our study highlights the therapeutic potential of miR-192-5p in enteritis by demonstrating its role in regulating autophagy and preserving IEB function. Targeting the miR-192-5p/Rictor axis is a promising approach for mitigating gut inflammatory injury and improving barrier integrity in enteritis patients.

The canonical Hippo pathway components modulate the differentiation of lamina propria regulatory T cells and T helper 17-like regulatory T cells in mouse colitis.

Regulatory T cells (Tregs) ameliorate inflammatory bowel diseases. However, their plasticity is not completely understood. In this study using a mouse colitis model, Tregs and T helper 17 (Th17)-like Tregs were detected and sorted using flow cytometry, followed by transcriptome sequencing, real-time RT-PCR, and flow cytometry to analyze the mRNA profiles of these cells. Treg plasticity was evaluated by in vitro differentiation assays. The immunosuppressive activities of Tregs and Th17-like Tregs were assessed in an adoptive transfer assay. We found Tregs-derived Th17-like Tregs in inflamed colonic lamina propria (LP). LP Th17-like Tregs expressed higher Th17-related cytokines and lower immunosuppressive cytokines compared with LP Tregs. Notably, Tregs expressed higher Yes-associated protein 1 (YAP1) but lower transcriptional coactivator with PDZ­binding motif (TAZ) than Th17-like Tregs. Verteporfin-mediated inhibition of YAP1 activity enhanced Th17-like Treg generation, whereas IBS008739-induced TAZ activation did not affect Th17-like Treg generation. Besides, verteporfin enhanced while IBS008739 suppressed the differentiation of Th17-like Tregs into Th17 cells. Furthermore, YAP1 activated STAT5 signaling in Tregs, whereas YAP1 and TAZ activated STAT3 and STAT5 signaling in Th17-like Tregs. Compared with Tregs, Th17-like Tregs were less efficacious in ameliorating colitis. Therefore, YAP1 suppressed Treg differentiation into Th17-like Tregs. Both YAP1 and TAZ inhibited the differentiation of Th17-like Tregs into Th17 cells. Therefore, YAP1 and TAZ probably maintain the immunosuppressive activities of Tregs and Th17-like Tregs in colitis.

FoxO1-modulated macrophage polarization regulates osteogenesis via PPAR-γ signaling.

Periodontitis, a common chronic inflammatory disease, epitomizes a significant impairment in the host immune system and an imbalance of bone metabolism. Macrophage polarization, a dynamic process dictated by the microenvironment, intricately contributes to the interplay between the immune system and bone remodeling, namely the osteoimmune system. Forkhead box protein O1 (FoxO1) has been shown to play a dramatic role in mediating oxidative stress, bone mass, as well as cellular metabolism. Nevertheless, the function and underlying mechanisms of FoxO1 in regulating macrophage polarization-mediated osteogenesis in periodontitis remain to be further elucidated. Here, we found that FoxO1 expression was closely linked to periodontitis, accompanied by aggravated inflammation. Notably, FoxO1 knockdown skewed macrophage polarization from M1 to the antiinflammatory M2 phenotype under inflammatory conditions, which rescued the impaired osteogenic potential. Mechanistically, we revealed that the enhancement of the transcription of peroxisome proliferator-activated receptor (PPAR) signaling in FoxO1-knockdown macrophages. In agreement with this contention, GW9662, a specific inhibitor of PPAR-γ signaling, greatly aggravated macrophage polarization from M2 to the M1 phenotype and attenuated osteogenic potential under inflammatory conditions. Additionally, PPAR-γ signaling agonist rosiglitazone (RSG) was applied to address ligature-induced periodontitis with attenuated inflammation. Our data lend conceptual credence to the function of FoxO1 in mediating macrophage polarization-regulated osteogenesis which serves as a novel therapeutic target for periodontitis.

A novel nanodrug for the sensitization of photothermal chemotherapy for breast cancer in vitro.

Owing to the complexity of tumor treatment, clinical tumor treatment has evolved from a single treatment mode to multiple combined treatment modes. Reducing the tolerance of tumors to heat and the toxicity of chemotherapy drugs to the body, as well as increasing the sensitivity of tumors to photothermal therapy and chemotherapy drugs, are key issues that urgently need to be addressed in the current cancer treatment. In this work, polylactic acid-based drug nanoparticles (PLA@DOX/GA/ICG) were synthesized with good photothermal conversion ability by encapsulating the water-soluble anticancer drug doxorubicin (DOX), photothermal conversion agent indocyanine green (ICG) and liposoluble drug gambogic acid (GA) using a double emulsion method. The preparation process of PLA@DOX/GA/ICG was examined. Gambogic acid entrapped in PLA@DOX/GA/ICG nanoparticles could act as an HSP90 protein inhibitor to achieve bidirectional sensitization to chemotherapy and photothermal therapy under 808 nm laser irradiation for the first time, effectively ablating breast cancer cells in vitro. This nanodrug was expected to be used for the efficient treatment of tumors.

Distinct Thalamo-Subcortical Circuits Underlie Painful Behavior and Depression-Like Behavior Following Nerve Injury.

Clinically, chronic pain and depression often coexist in multiple diseases and reciprocally reinforce each other, which greatly escalates the difficulty of treatment. The neural circuit mechanism underlying the chronic pain/depression comorbidity remains unclear. The present study reports that two distinct subregions in the paraventricular thalamus (PVT) play different roles in this pathological process. In the first subregion PVT posterior (PVP), glutamatergic neurons (PVPGlu) send signals to GABAergic neurons (VLPAGGABA) in the ventrolateral periaqueductal gray (VLPAG), which mediates painful behavior in comorbidity. Meanwhile, in another subregion PVT anterior (PVA), glutamatergic neurons (PVAGlu) send signals to the nucleus accumbens D1-positive neurons and D2-positive neurons (NAcD1→D2), which is involved in depression-like behavior in comorbidity. This study demonstrates that the distinct thalamo-subcortical circuits PVPGlu→VLPAGGABA and PVAGlu→NAcD1→D2 mediated painful behavior and depression-like behavior following spared nerve injury (SNI), respectively, which provides the circuit-based potential targets for preventing and treating comorbidity.

Prediction of frequency response of sub-frame bushing and study of high-order fractional derivative viscoelastic model.

This paper presents experimental and dynamic modeling research on the rubber bushings of the rear sub-frame. The Particle Swarm Optimization algorithm was utilized to optimize a Backpropagation (BP) neural network, which was separately trained and tested across two frequency ranges: 1-40 Hz and 41-50 Hz, using wideband frequency sweep dynamic stiffness test data. The testing errors at amplitudes of 0.2 mm, 0.3 mm, and 0.5 mm were found to be 1.03%, 3.05%, and 1.96%, respectively. Subsequently, the trained neural network was employed to predict data within the frequency range of 51-70 Hz. To incorporate the predicted data into simulation software, a dynamic model of the rubber bushing was established, encompassing elastic, friction, and viscoelastic elements. Additionally, a novel model, integrating high-order fractional derivatives, was proposed based on the frequency-dependent model for the viscoelastic element. An enhanced Particle Swarm Optimization algorithm was introduced to identify the model's parameters using the predicted data. In comparison to the frequency-dependent model, the new model exhibited lower fitting errors at various amplitudes, with reductions of 3.84%, 3.61%, and 5.49%, respectively. This research establishes a solid foundation for subsequent vehicle dynamic modeling and simulation.

An enantioselective fluorescent probe for detecting arginine and glutamic acids.

Amino acids are important chiral compounds in the human body, and are important basic components that make up the human body and play an important role in the human body. Among them, different enantiomers of an amino acid may have different roles, and different types of amino acids can be interconverted. However, the content of D-amino acids is much lower than that of L-amino acids, which is difficult to be detected. At present, many of the potential roles of D-amino acids, such as the conversion of D-amino acids to each other, have not yet been fully revealed. Hence, we synthesized fluorescent probe (R)-5 by condensation of 1,1'-Bi-2-naphthol (BINOL) and 2-(Aminomethyl)pyridine with Schiff base, which can recognize both D-arginine and D-glutamic acid at low concentrations. Meanwhile, (R)-5 can be applied to paper-based sensors for the detection of arginine and glutamate in living cells and for food amino acid detection.

TMEM52B Isoforms P18 and P20 Differentially Promote the Oncogenesis and Metastasis of Nasopharyngeal Carcinoma.

Transmembrane protein 52B (TMEM52B), a newly identified tumor-related gene, has been reported to regulate various tumors, yet its role in nasopharyngeal carcinoma (NPC) remains unclear. Transcriptomic analysis of NPC cell lines reveals frequent overexpression of TMEM52B, and immunohistochemical results show that TMEM52B is associated with advanced tumor stage, recurrence, and decreased survival time. Depleting TMEM52B inhibits the proliferation, migration, invasion, and oncogenesis of NPC cells in vivo. TMEM52B encodes two isoforms, TMEM52B-P18 and TMEM52B-P20, differing in their N-terminals. While both isoforms exhibit similar pro-oncogenic roles and contribute to drug resistance in NPC, TMEM52B-P20 differentially promotes metastasis. This functional discrepancy may be attributed to their distinct subcellular localization; TMEM52B-P18 is confined to the cytoplasm, while TMEM52B-P20 is found both at the cell membrane and in the cytoplasm. Mechanistically, cytoplasmic TMEM52B enhances AKT phosphorylation by interacting with phosphoglycerate kinase 1 (PGK1), fostering NPC growth and metastasis. Meanwhile, membrane-localized TMEM52B-P20 promotes E-cadherin ubiquitination and degradation by facilitating its interaction with the E3 ubiquitin ligase NEDD4, further driving NPC metastasis. In conclusion, the TMEM52B-P18 and TMEM52B-P20 isoforms promote the metastasis of NPC cells through different mechanisms. Drugs targeting these TMEM52B isoforms may offer therapeutic benefits to cancer patients with varying degrees of metastasis.

Robust Transparent Photothermal Omniphobic Coating for Efficient Anti/Deicing and Antifogging.

Icing and fogging on optical material surfaces bring various problems in daily life. Recently, some photothermal coatings have been reported to prevent the condensation or freeze of water droplets by increasing the surface temperature. However, it is a great challenge to apply them in practical conditions due to their opaqueness and poor mechanical wear-resistant property. In this work, we constructed a robust transparent photothermal omniphobic coating with a simple dip-coating technique. In the coating system, photothermal polypyrrole nanoparticles are introduced into inorganic silica networks, and then polydimethylsiloxane (PDMS) brushes were grafted on the inorganic silica layer to endow the surface with omniphobicity and stain resistance. The transparency and photothermal capacity of the coating can be regulated by the deposition times of the coating. In addition, the coating has an excellent anti/deicing property and reduces ice adhesion obviously due to the existence of "liquid-like" PDMS brushes. More importantly, the coating presents outstanding mechanical wear-resistant and self-lubricating properties that can endure several thousand friction cycles without performance loss. The mechanically robust photothermal omniphobic coating gives a feasible approach to anti-icing and antifogging of transparent substrates under sunlight irradiation.

Association between gut microbiota and acute pancreatitis: a bidirectional Mendelian randomization study.

BACKGROUND AND AIM: The dysbiosis of gut microbiota has been reported in acute pancreatitis. However, the direction and magnitude between host microbiota and pancreas remains to be established. This study investigated the association between gut microbiota and acute pancreatitis using Mendelian randomization (MR) methods. METHODS: Summary statistics of gut microbiota abundance and acute pancreatitis were extracted from genome-wide association studies (GWAS). The two-sample bidirectional MR design was employed to assess genetic association between the microbiota and pancreatitis, followed by a comprehensive sensitivity analysis to verify the robustness of the results. RESULTS: Seven microbiota taxa have been identified as significantly associated with the development of pancreatitis. Host genetic-driven order Bacteroidales and class Bacteroidia are associated with an increased risk of pancreatitis. The genera Coprococcus and Eubacterium fissicatena group also exhibit a positive effect on the development of pancreatitis, while the genera Prevotella, Ruminiclostridium, and Ruminococcaceae act as protective factors against pancreatitis. In contrast, acute pancreatitis was positively correlated with phylum Proteobacteria and genus Lachnospiraceae and negatively correlated with genus Holdemania. CONCLUSIONS: The bidirectional relationship between gut microbiota and acute pancreatitis suggests a critical role for host-microbiota crosstalk in the development of the disease. Targeted modulation of specific gut microbiota enables the prevention and treatment of acute pancreatitis.

Motico: An attentional mechanism network model for smart aging disease risk prediction based on image data classification.

The current disease risk prediction model with many parameters is complex to run smoothly on mobile terminals such as tablets and mobile phones in imaginative elderly care application scenarios. In order to further reduce the number of parameters in the model and enable the disease risk prediction model to run smoothly on mobile terminals, we designed a model called Motico (An Attention Mechanism Network Model for Image Data Classification). During the implementation of the Motico model, in order to protect image features, we designed an image data preprocessing method and an attention mechanism network model for image data classification. The Motico model parameter size is only 5.26 MB, and the memory only takes up 135.69 MB. In the experiment, the accuracy of disease risk prediction was 96 %, the precision rate was 97 %, the recall rate was 93 %, the specificity was 98 %, the F1 score was 95 %, and the AUC was 95 %. This experimental result shows that our Motico model can implement classification prediction based on the image data classification attention mechanism network on mobile terminals.

Kaolin-Derived Porous Silico-Aluminate Nanoparticles as Absorbents for Emergency Disposal of Toluene Leakage.

To rapidly eliminate toluene from aqueous environments during leakage accidents, this paper synthesized porous silico-aluminate nanoparticles (SANs) via a hydrothermal method, using cost-effective and non-toxic natural kaolin as the basic raw material. The morphology and structure of the porous SANs were characterized using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and BET-specific surface area tests. The effects of different conditions, such as the dosage of porous SANs, initial concentration of toluene, temperature, capture time, and pH, on the adsorption performance of porous SANs were analyzed. The as-prepared SANs exhibited a high removal efficiency and rapid adsorption performance toward toluene in aqueous solution. Finally, the kinetics of the adsorption of toluene in aqueous solution by porous SANs were investigated. The mechanism of the adsorption of toluene by porous SANs was further discussed. These findings provide a cost-effective and highly efficient absorbent for the emergency disposal of toluene leakage accidents.

Eruptive xanthomas in a patient with severe hypertriglyceridemia: A case report.

BACKGROUND: Xanthomatosis, a metabolic disorder causing yellow growths (xanthomas), poses challenges in lipid metabolism. This case study introduces the first documented instance within China's Yi population, emphasizing the need to explore dietary habits and treatment strategies tailored to this specific community. CASE SUMMARY: Xanthomatosis is a metabolic disorder where lipid metabolism goes awry, resulting in the development of yellowish growths called xanthomas. A male patient, 47 years of age, from China's Yi population, who is obese, visited our dermatology clinic complaining of widespread, non-painful rashes that have been present for two weeks. The patient works as a chef and has a diet that frequently includes oily and greasy foods. This case represents the initial documentation of xanthomatosis within the Yi population in China, offering a theoretical foundation for understanding dietary patterns and treatment options specific to the Yi community. CONCLUSION: The first report of xanthomatosis in the Yi population in China lays a theoretical foundation for understanding Yi dietary patterns and treatment.

Potential mechanisms of hexaconazole resistance in Fusarium graminearum.

The Fusarium head blight (FHB) caused by Fusarium graminearum is a serious fungal disease that can dramatically impact wheat production. At present, control is mainly achieved by the use of chemical fungicides. Hexaconazole (IUPAC name: 2-(2,4-dichlorophenyl)-1-(1,2,4-triazol-1-yl)hexan-2-ol) is a widely used triazole fungicide, but the sensitivity of F. graminearum to this compound has yet to be established. The current study found that the EC50 values of 83 field isolates of F. graminearum ranged between 0.06 and 4.33 µg/mL, with an average EC50 of 0.78 µg/mL. Assessment of four hexaconazole-resistant laboratory mutants of F. graminearum revealed that their mycelial growth, and pathogenicity were reduced compared to their parental isolates, and that asexual reproduction was reduced by resistance to hexaconazole. Meanwhile, the mutants appeared to be more sensitive to abiotic stress associated with SDS, and H2O2, while their tolerance of high concentration of Congo red, and Na+ and K+ increased. Molecular analysis revealed numerous point mutations in the FgCYP51 target genes that resulted in amino acid substitutions, including L92P and N123S in FgCYP51A, as well as M331V, F62L, Q252R, A412V, and V488A in FgCYP51B, and S28L, S256A, V307A, D287G and R515I in FgCYP51C, three of which (S28L, S256A, and V307A) were conserved in all of the resistant mutants. Furthermore, the expression of the FgCYP51 genes in resistant strains was found to be significantly (p < 0.05) reduced compared to their sensitive parental isolates. Positive cross-resistance was found between hexaconazole and metconazole and flutriafol, as well as with the diarylamine fungicide fluazinam, but not with propiconazole, and the phenylpyrrole fungicide fludioxonil, or with tebuconazole, which actually exhibited negative cross-resistance. These results provide valuable insight into resistant mechanisms to triazole fungicides in F. graminearum, as well as the appropriate selection of fungicide combinations for the control of FHB to ensure optimal wheat production.

Comparative analysis of risk factors associated with degeneration of adjacent segments: zero-profile anchored spacer vs. anterior cervical plate and cage construct.

Objective: Anterior cervical discectomy and fusion (ACDF) is an established treatment for cervical degenerative disc disease, but cervical spine surgery may affect sagittal alignment parameters and induce adjacent segment degeneration (ASD). This study aimed to determine the risk factors for developing ASD following anterior cervical plate and cage (ACPC) compared with the use of zero-profile anchored spacer (ROI-C). Methods: A retrospective contrastive study included 105 patients who underwent ACPC or ROI-C between January 2014 and October 2019 at our treatment centre. There were 50 cases in the ROI-C group and 55 patients in the ACPC group. Clinical and radiological results and the incidence of ASD were assessed after surgery. All patients were further divided into the ASD and non-ASD groups for subgroup analysis. Results: At each follow-up time, there was no statistically significant in radiographic parameters between the two groups. The overall ASD rate was higher in the ACPC group than in the ROI-C group (65.5% vs. 44.0%, p = 0.027). The low preoperative Cobb angle, low preoperative segment angle (SA), and loss of Cobb (ΔCobb) were significantly correlated with ASD. However, clinical outcomes were not associated with ASD at any postoperative follow-up visit. Conclusion: Equally good therapeutic effects were achieved with both the ROI-C and ACPC. The occurrence of ASD was considerably higher in the ACPC group than in the ROI-C group. The preoperative Cobb angle, preoperative SA, and ΔCobb were the most associated with an increase in the risk of ASD.

Current status and research progress of minimally invasive treatment of glioma.

Glioma has a high malignant degree and poor prognosis, which seriously affects the prognosis of patients. Traditional treatment methods mainly include craniotomy tumor resection, postoperative radiotherapy and chemotherapy. Although above methods have achieved remarkable curative effect, they still have certain limitations and adverse reactions. With the introduction of the concept of minimally invasive surgery and its clinical application as well as the development and progress of imaging technology, minimally invasive treatment of glioma has become a research hotspot in the field of neuromedicine, including photothermal treatment, photodynamic therapy, laser-induced thermal theraphy and TT-Fields of tumor. These therapeutic methods possess the advantages of precision, minimally invasive, quick recovery and significant curative effect, and have been widely used in clinical practice. The purpose of this review is to introduce the progress of minimally invasive treatment of glioma in recent years and the achievements and prospects for the future.

Metasurface optical trap array for single atoms.

Metasurfaces made of subwavelength silicon nanopillars provide unparalleled capacity to manipulate light, and have emerged as one of the leading platforms for developing integrated photonic devices. In this study, we report on a compact, passive approach based on planar metasurface optics to generate large optical trap arrays. The unique configuration is achieved with a meta-hologram to convert a single incident laser beam into an array of individual beams, followed up with a metalens to form multiple laser foci for single rubidium atom trapping. We experimentally demonstrate two-dimensional arrays of 5 × 5 and 25 × 25 at the wavelength of 830 nm, validating the capability and scalability of our metasurface design. Beam waists ∼1.5 µm, spacings (about 15 µm), and low trap depth variations (8%) of relevance to quantum control for an atomic array are achieved in a robust and efficient fashion. The presented work highlights a compact, stable, and scalable trap array platform well-suitable for Rydberg-state mediated quantum gate operations, which will further facilitate advances in neutral atom quantum computing.

Fabrication of Poly(ionic liquid) Hydrogels Incorporating Liquid Metal Microgels for Enhanced Synergistic Antifouling Applications.

Hydrogels are ideal for antifouling materials due to their high hydrophilicity and low adhesion properties. Herein, poly(ionic liquid) hydrogels integrated with zwitterionic copolymer-functionalized gallium-based liquid metal (PMPC-GLM) microgels were successfully prepared by a one-pot reaction. Poly(ionic liquid) hydrogels (IL-Gel) were obtained by chemical cross-linking the copolymer of ionic liquid, acrylic acid, and acrylamide, and the introduction of ionic liquid (IL) significantly increased the cross-linking density; this approach consequently enhanced the mechanical and antiswelling properties of the hydrogels. The swelling ratio of IL-Gel decreased eight times compared to the original hydrogels. PMPC-GLM microgels were prepared through grafting the zwitterionic polymer PMPC onto the GLM nanodroplet surface, which exhibited efficient antifouling performance attributed to the bactericidal effect of Ga3+ and the antibacterial effect of the zwitterionic polymer layer PMPC. Based on the synergistic effect of PMPC-GLM microgels and IL, the composite hydrogels PMPC-GLM@IL-Gel not only exhibited excellent mechanical and antiswelling properties but also showed outstanding antibacterial and antifouling properties. Consequently, PMPC-GLM@IL-Gel hydrogels achieved inhibition rates of over 90% against bacteria and more than 85% against microalgae.

Enhancing Molecular Energy Predictions with Physically Constrained Modifications to the Neural Network Potential.

Exclusively prioritizing the precision of energy prediction frequently proves inadequate in satisfying multifaceted requirements. A heightened focus is warranted on assessing the rationality of potential energy curves predicted by machine learning-based force fields (MLFFs), alongside evaluating the pragmatic utility of these MLFFs. This study introduces SWANI, an optimized neural network potential stemming from the ANI framework. Through the incorporation of supplementary physical constraints, SWANI aligns more cohesively with chemical expectations, yielding rational potential energy profiles. It also exhibits superior predictive precision compared with that of the ANI model. Additionally, a comprehensive comparison is conducted between SWANI and a prominent graph neural network-based model. The findings indicate that SWANI outperforms the latter, particularly for molecules exceeding the dimensions of the training set. This outcome underscores SWANI's exceptional capacity for generalization and its proficiency in handling larger molecular systems.