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As urbanization accelerates and buildings become more complex, fire emergency evacuation has become increasingly challenging. Traditional evacuation plans often struggle with slow response times and suboptimal path planning in real-time dynamic and complex fire scenarios. To address these issues, this study proposes the IoT-based DWM-Evac model for fire emergency evacuation path planning. The model leverages IoT technology by using various sensors placed inside buildings to monitor fire incidents and spread in real-time, collecting critical data such as temperature, smoke concentration, and flame location. It integrates Dynamic Graph Neural Networks (DGNN), Whale Optimization Algorithm (WOA), and Markov Decision Process (MDP) to enhance path efficiency and safety. Experimental results indicate that the DWM-Evac model achieves an average evacuation time of 315 s in a virtual mall environment, 25 s shorter than traditional plans, with an average path length of 255 meters and a path safety score of 0.92, higher than the traditional plan’s 0.88. The application of IoT in fire emergency management not only improves response speed but also optimizes path planning, significantly enhancing personnel safety.

Transjugular intrahepatic portosystemic shunt (TIPS) is an essential procedure for the treatment of portal hypertension but can result in hepatic encephalopathy (HE), a serious complication that worsens patient outcomes. Investigating predictors of HE after TIPS is essential to improve prognosis. This review analyzes risk factors and compares predictive models, weighing traditional scores such as Child-Pugh, Model for End-Stage Liver Disease (MELD), and albumin-bilirubin (ALBI) against emerging artificial intelligence (AI) techniques. While traditional scores provide initial insights into HE risk, they have limitations in dealing with clinical complexity. Advances in machine learning (ML), particularly when integrated with imaging and clinical data, offer refined assessments. These innovations suggest the potential for AI to significantly improve the prediction of post-TIPS HE. The study provides clinicians with a comprehensive overview of current prediction methods, while advocating for the integration of AI to increase the accuracy of post-TIPS HE assessments. By harnessing the power of AI, clinicians can better manage the risks associated with TIPS and tailor interventions to individual patient needs. Future research should therefore prioritize the development of advanced AI frameworks that can assimilate diverse data streams to support clinical decision-making. The goal is not only to more accurately predict HE, but also to improve overall patient care and quality of life.

Introduction: Current anti-rheumatic drugs are primarily modulating immune cell activation, yet their effectiveness remained suboptimal. Therefore, novel therapeutics targeting alternative mechanisms, such as synovial activation, is urgently needed. Objectives: To explore the role of Midline-1 (Mid1) in synovial activation. Methods: NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice were used to establish a subcutaneous xenograft model. Wild-type C57BL/6, Mid1-/-, Dpp4-/-, and Mid1-/- Dpp4-/- mice were used to establish a collagen-induced arthritis model. Cell viability, cell cycle, qPCR and western blotting analysis were used to detect MH7A proliferation, dipeptidyl peptidase-4 (DPP4) and Mid1 levels. Co-immunoprecipitation and proteomic analysis identified the candidate protein of Mid1 substrates. Ubiquitination assays were used to determine DPP4 ubiquitination status. Results: An increase in Mid1, an E3 ubiquitin ligase, was observed in human RA synovial tissue by GEO dataset analysis, and this elevation was confirmed in a collagen-induced mouse arthritis model. Notably, deletion of Mid1 in a collagen-induced arthritis model completely protected mice from developing arthritis. Subsequent overexpression and knockdown experiments on MH7A, a human synoviocyte cell line, unveiled a previously unrecognized role of Mid1 in synoviocyte proliferation and migration, the key aspects of synovial activation. Co-immunoprecipitation and proteomic analysis identified DPP4 as the most significant candidate of Mid1 substrates. Mechanistically, Mid1 promoted synoviocyte proliferation and migration by inducing ubiquitin-mediated proteasomal degradation of DPP4. DPP4 deficiency led to increased proliferation, migration, and inflammatory cytokine production in MH7A, while reconstitution of DPP4 significantly abolished Mid1-induced augmentation of cell proliferation and activation. Additionally, double knockout model showed that DPP4 deficiency abolished the protective effect of Mid1 defect on arthritis. Conclusion: Overall, our findings suggest that the ubiquitination of DPP4 by Mid1 promotes synovial cell proliferation and invasion, exacerbating synovitis in RA. These results reveal a novel mechanism that controls synovial activation, positioning Mid1 as a promising target for therapeutic intervention in RA.

Pien Tze Huang (PZH), a class-1 nationally protected traditional Chinese medicine (TCM), has been used to treat liver diseases such as hepatitis; however, the effect of PZH on the progression of sepsis is unknown. Here, we reported that PZH attenuated lipopolysaccharide (LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signalling. Mechanistically, PZH stimulated signal transducer and activator of transcription 3 (STAT3) phosphorylation to induce the expression of A20, which could inhibit the activation of NF-κB and MAPK signalling. Knockdown of the bile acid (BA) receptor G protein-coupled bile acid receptor 1 (TGR5) in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction, as well as the LPS-induced inflammatory response, suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5. Consistently, deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20, the activation of NF-κB and MAPK signalling, and the production of proinflammatory cytokines, whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines. Overall, our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

Summary: Autophagy is an essential degradation and recycling process that maintains cellular homeostasis during stress or nutrient deprivation. However, certain types of tumors such as pancreatic cancers can circumvent autophagy inhibition to sustain growth. The mechanism that autophagy-deficient pancreatic ductal adenocarcinoma (PDAC) uses to grow under nutrient deprivation is poorly understood. Our data show that nutrient deprivation in PDAC results in UDP-glucose dehydrogenase (UGDH) degradation, which is dependent on autophagic cargo receptor sequestosome 1 (p62). Moreover, we demonstrate that accumulated UGDH is indispensable for autophagy-deficient PDAC cells proliferation by promoting hyaluronic acid (HA) synthesis upon energy deprivation. Using an orthotopic mouse model of PDAC, we find that inhibition of HA synthesis by targeting UGDH in PDAC reduces tumor weight. Thus, the combined inhibition of HA and autophagy might be an attractive strategy for PDAC treatment.

Summary: Cells maintain and dynamically change their proteomes according to the environment and their needs. Mechanistic target of rapamycin (mTOR) is a key regulator of proteostasis, homeostasis of the proteome. Thus, dysregulation of mTOR leads to changes in proteostasis and the consequent progression of diseases, including cancer. Based on the physiological and clinical importance of mTOR signaling, we investigated mTOR feedback signaling, proteostasis, and cell fate. Here, we reveal that mTOR targeting inhibits eIF4E-mediated cap-dependent translation, but feedback signaling activates a translation initiation factor, eukaryotic translation initiation factor 3D (eIF3D), to sustain alternative non-canonical translation mechanisms. Importantly, eIF3D-mediated protein synthesis enables cell phenotype switching from proliferative to more migratory. eIF3D cooperates with mRNA-binding proteins such as heterogeneous nuclear ribonucleoprotein F (hnRNPF), heterogeneous nuclear ribonucleoprotein K (hnRNPK), and Sjogren syndrome antigen B (SSB) to support selective mRNA translation following mTOR inhibition, which upregulates and activates proteins involved in insulin receptor (INSR)/insulin-like growth factor 1 receptor (IGF1R)/insulin receptor substrate (IRS) and interleukin 6 signal transducer (IL-6ST)/Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling. Our study highlights the mechanisms by which cells establish the dynamic change of proteostasis and the resulting phenotype switch.

Sepsis is a systemic inflammatory response to infection, where sepsis-associated acute kidney injury (AKI) is a common morbid disease with a high morbidity and mortality, and however at present no effective therapy exists. Increasing evidence have shown that mitochondrial damage and inflammatory response are important initiating factors in pathogenesis of septic AKI. Natural flavonoid pectolinarigenin exerted anti-inflammatory properties in previous studies, while its role in septic AKI remains unknown. In the study, pectolinarigenin administration significantly ameliorated the dramatic rise of serum creatinine and blood urea nitrogen in lipopolysaccharide (LPS)- and cecal ligation/puncture (CLP)-induced septic mice, respectively. Consistently, LPS/CLP-induced renal damage as implied by histopathological score and the increased injury markers NGAL and KIM-1, which was attenuated by pectolinarigenin. Meanwhile, LPS/CLP triggered proinflammatory cytokine production and inflammation related proteins in the kidneys. However, pectolinarigenin inhibited renal expression of IL-6, IL-1β, TNF-α, and MCP-1 to improve inflammatory response. Furthermore, pectolinarigenin upregulated Bcl-2 protein expression and suppressed apoptotic protein of BAX and cleaved caspase-3 in the kidneys of CLP-induced septic AKI. Mechanistically, LPS could induce the high expression of IL-6 and trigger the phosphorylation of Jak2 and Stat3, while pectolinarigenin remarkably reduced their corresponding levels. Notably, CLP-induced kidney injury of mice significantly reduced the expression of PGC-1α, OPA1 and increased the expression of Drp1, Cyt-C, where pectolinarigenin pretreatment significantly restored their corresponding expression in mice. In summary, pectolinarigenin improved septic AKI via inhibiting JAK2/STAT3 signaling and mitochondria dysfunction.

The safe operating area is an operating area with high reliability for SiC MOSFET, and its degradation may cause power electronic system failure. The safe-operating-area degradation and the failure modes of 1200 V/66A SiC MOSFET caused by repetitive short-circuit stress with different short-circuit durations and repetition rates are investigated. A short circuit test platform with circuit protection is configured to degrade DUT(device under test), and the safe operating area is characterized after repetitive short circuit stress is applied. The degradation mechanism of the safe operating area is explained by the 1-D electro-thermal coupling model based on Sentaurus TCAD. When the critical short-circuit duration is 12μs, the single short-circuit failure mode of DUT with 400 V dc-bus voltage is a gate-source short-circuit failure. From the short circuit test result, the failure modes under repetitive short-circuit conditions include gate-source short-circuit failure and thermal runaway, depending on the repetitive rates. For the same short-circuit time interval, when the short-circuit duration is 10μs, the weakest boundary of the safe operating area is the blocking voltage. When the short-circuit duration is 2μs, all three boundaries of the safe operating area are contracted. These results are confined to 400 V dc-bus voltage, 25 °C case temperature, and 18 V/-3 V gate-source voltage.

In the last few decades, short-chain chlorinated paraffins (SCCPs) have become the most heavily produced monomeric organohalogen compounds, and have been reported to induce multiple organ toxicity. However, the effects of SCCPs on the central nervous system are unknown. In the present study, we show that SCCP exposure induced astrocyte proliferation and increased the expression of two critical markers of astrocyte activation, glial fibrillary acidic protein and inducible nitric oxide synthase, in vivo and in vitro. SCCP exposure also increased inflammatory factory gene expression. Moreover, SCCP treatment triggered Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signalling, as shown by increased phosphorylation and STAT3 translocation to the nucleus. Both JAK2 and STAT3 inhibition effectively attenuated SCCP-induced astrocyte activation. Finally, JAK2 inhibition significantly rescued STAT3 phosphorylation and nuclear translocation. Taken together, JAK2/STAT3 pathway activation contributed to SCCP-induced astrocyte activation. These data will help elucidate the molecular mechanism underlying SCCP-induced neurotoxicity.

Objective: Bone regeneration involves a coordinated cascade of events that are regulated by several cytokines and growth factors, among which bone morphogenic protein-2 (BMP-2), vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) play important roles. In this study, we investigated the effects of dual release of the three growth factors on bone regeneration in femur defects. Methods: A composite consisting of Gelatin microparticles loaded with VEGF/FGF-2 and poly(lactic-co-glycolic acid)-poly(ethylene glycol)-carboxyl (PLGA-PEG-COOH) microparticles loaded with BMP-2 encapsulated in a nano hydroxyapatite-poly actic-co-glycolic acid (nHA-PLGA) scaffold was prepared for the dual release of the growth factors. Results: On the 14th day, decreased release rate of BMP-2 compared with FGF-2 and VEGF was observed. However, after 14 days, compared to FGF-2 and VEGF, BMP-2 showed an increased release rate. Controlled dual release of BMP-2 and VEGF, FGF-2 resulted in a significant osteogenic differentiation of bone mesenchymal stem cells (BMSCs). Moreover, effects of the composite scaffold on functional connection of osteoblast-vascular cells during bone development were evaluated. The synergistic effects of dual delivery of growth factors were shown to promote the expression of VEGF in BMSCs. Increased secretion of VEGF from BMSCs promoted the proliferation and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) in the co-culture system. At 12 weeks after implantation, blood vessel and bone formation were analyzed by micro-CT and histology. The composite scaffold significantly promoted the formation of blood vessels and new bone in femur defects. Conclusions: These findings demonstrate that dual delivery of angiogenic factors and osteogenic factors from Gelatin and PLGA-PEG-COOH microparticles-based composite scaffolds exerted an osteogenic-angiogenic coupling effect on bone regeneration. This approach will inform on the development of appropriate designs of high-performance bioscaffolds for bone tissue engineering.

The engineering stress–strain curve of a material allows one to determine mechanical properties such as elastic modulus, strength, and toughness. While machine learning has recently been used to predict stress–strain curves, large volumes of experimental data are required to achieve high prediction accuracy. More importantly, conventional machine learning models are not generalizable from one material to another. To address this issue, a novel transfer learning approach is introduced to predict stress–strain curves across different fiber reinforced polymer (FRP) composites fabricated via additive manufacturing. Optimal transport (OT) is integrated with the transfer learning approach by mapping the source label space to the target label space, which further improves knowledge transferability across different FRP composites. The stress–strain curves of the additively manufactured FRP composites are generated under flexural loading conditions. Experimental results show that the OT-integrated transfer learning approach can predict the complex stress–strain curves of FRP composites with small training data. The predictive model achieved a mean absolute percentage error (MAPE) of less than 10%. The extracted modulus and strength from the predicted stress–strain curves achieved MAPEs of less than 5% and 10%, respectively. This work demonstrates that transfer learning has the potential to transform how stress–strain curves are generated.

Modern engineering applications require advanced materials that are stronger, tougher, and lighter. Nature offers various structural architectures to achieve superior mechanical properties. Inspired by bone with a spongy soft-core and a compact hard-shell, this study introduces architected multi-material lattices with tunable mechanical properties such as stiffness, strength, and energy absorption. The architected lattices are fabricated via multi-material fused filament fabrication. The hard polylactic acid (PLA) shell of the lattice struts maintains the stiffness, while the soft thermoplastic polyurethane (TPU) core enhances toughness and energy absorption capacity. The microstructural and mixed-mode fracture characteristics of the PLA-TPU interfaces were examined since the interfacial microstructure and adhesion are crucial to stress transfer in multi-phase composite materials. This study explores the flexural behavior of the multi-material struts and reveals two distinct failure modes depending on the volume fraction of the soft-core through 3-point bend tests. This study demonstrates the bio-inspired design on a hexagonal planar lattice with a strut thickness-to-length ratio of 0.3. Tunable stiffness, strength, and energy absorption are achieved by varying the core-to-strut thickness ratio. Compression test results show that the architected lattices exhibit an energy absorption capacity that is about 2–3 times greater than that of the constituent single-phase lattices.

In this article, we provide an in-depth review of important works on phase segregation which occurs as a result of mixing organic semiconductors with polymeric additives. Throughout the discussion, the indispensable correlations among phase segregation, crystal growth, layer structure and film morphology are showcased using specific examples that mainly entail small-molecule organic semiconductors such as 6,13-bis(triisopropylsilylethynyl) pentacene (TIPS pentacene) and 2,8-difluoro-5,11-bis(triethylsilylethynyl)anthradithiophene (diF-TES-ADT). The various factors that impact the phase segregation are analyzed, which include surface energy, solvent choice, additive nature, and substrate interaction. The beneficial effects of phase segregation on charge transport and operational stabilities of organic semiconductor based organic thin film transistors (OTFTs) are also assessed. We believe that the phase segregation examples discussed in this work shed light on optimizing the electrical performance of organic semiconductors and unlock favorable features useful for their application in high-performance organic electronics on flexible substrates.

In this study, we report on an effective approach to modulate crystallization, control charge transport and enhance performance consistency of small-molecule semiconductor based organic thin film transistors (OTFTs) with the addition of a polyacrylate polymer additive poly(2-ethylhexyl acrylate) (P2EHA). 6,13-bis(triisopropylsilylethynyl) pentacene (TIPS pentacene) was used as a benchmark semiconductor to blend with the P2EHA additive, leading to a vertical phase separation between these two components. The resultant TIPS pentacene film exhibited greatly reduced crystal misorientation, enlarged grain width and enhanced film coverage. Bottom-gate, bottom-contact OTFTs based on the TIPS pentacene/P2EHA blends were fabricated and showed an increased average hole mobility of 0.317 ± 0.047 cm2/V, as well as a performance consistency factor of 6.72, which is defined as the ratio of the average hole mobility to the standard deviation of mobility. Notably, it leads to a 10-fold and 7-fold enhancement of average mobility and performance consistency as compared to the pristine TIPS pentacene OTFTs. This great improvement of device performance can be attributed to the reduced crystal misorientation, less defects and trap centers at the grain boundaries as a result of the enlarged grain width, as well as increased film coverage, due to the addition of the P2EHA polyacrylate polymer additive. Keywords: Small-molecule semiconductor, Polymer additive, Charge transport, Organic thin film transistors, Organic electronics

Summary: Many methods exist for the synthesis of covalent organic frameworks (COFs), but precise morphology control allowing the tailoring of core-shell and yolk-shell nanostructures has been elusive, mainly due to poor control of the reaction-diffusion processes. Herein, we propose the precise regulation of the COF generation and decomposition rates and their relationship with the diffusion rate of COF species during the synthesis, which enables a successful preparation of core-shell, yolk-shell, hollow-spherical, and multiple yolk-shell COF structures with tunable sizes ranging from 200 to 1,400 nm. Formed COF structures can serve as nanoreactors or nanocontainers, with the shell layer providing molecular-size selectivity determined by the nanopore size demonstrated here using Suzuki coupling reactions with phenylboronic acid, which produce a size-cutoff efficiency for halogenated aromatics approaching 100%. The precise morphology design and control of COF particles and hybrids may help enhance application efficiencies and provide access to new functionalities for COF materials.