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This study aims to improve the market efficiency of intellectual property pledge financing, based on the perspective of willingness to perform of technology-based SMEs, this paper defined the end-of-period value conversion coefficient of pledged property (EVCC) to measure the comparative relationship between the end-of-period value of the pledged intellectual property and the sum of principal and interest of the loan and introduced it into the game payment matrix; using evolutionary game theory, based on the assumption of bounded rationality, an evolutionary game model of intellectual property pledge financing between technology-based SMEs and banks based on the EVCC was constructed, and a numerical simulation was then conducted. The results of asymptotic stability analysis showed that when a certain condition is met, the strategy combination (performance, loan) is the evolutionary stability strategy (ESS). The numerical simulation showed that the EVCC has a positive impact on the speed of technology-based SMEs choosing the performance strategy, and there is a positive threshold effect (The threshold is 0.90). The initial value of pledged intellectual property has a negative impact on the speed of technology-based SMEs choosing the performance strategy, and there is a reverse threshold effect (The threshold is 1250), as well as the pledge rate of intellectual property (The threshold is 0.375). However, the loan interest rate has no significant impact on the strategic choice of technology-based SMEs. In addition, the EVCC has no significant impact on the banks’ strategy choice. The initial value of pledged intellectual property has a negative impact on the speed of banks choosing loan strategies, and there is a reverse threshold effect (The threshold is 1250). The pledge rate of intellectual property has an inverted U-shaped impact on the speed of banks choosing loan strategies ( ω * may be close to 0.30), and there is a reverse threshold effect (The threshold is 0.375). The loan interest rate has a positive impact on the speed of banks choosing loan strategies, and there is a positive threshold effect (The threshold is 0.03). In addition, the trustworthy joint incentive not only has a positive impact on the speed of technology-based SMEs choosing the performance strategy, but also has a positive impact on the speed of banks choosing the loan strategy, and both have a positive threshold effect (The threshold for both is 15), as well as the dishonesty joint punishment (The threshold for both is 85). This model enriches the multi-agent game theory framework of intellectual property pledge financing. The numerical simulation results can provide a decision-making reference for technology-based SMEs and banks to formulate intellectual property pledge financing strategies.

Antimicrobial peptides (AMPs) have recently attracted a great deal of attention as promising antibiotic candidates, but some obstacles such as toxicity and high synthesis cost must be addressed before developing them further. For developing short peptides with improved cell selectivity, we designed a series of modified PMAP-36 analogues. Antimicrobial assays showed that decreasing chain length in a certain range retained the high antimicrobial activity of the parental peptide and reduced hemolysis. The 18-mer peptide RI18 exhibited excellent antimicrobial activity against both bacteria and fungi, and its hemolytic activity was observably lower than PMAP-36 and melittin. The selectivity indexes of RI18 against bacteria and fungi were improved approximately 19-fold and 108-fold, respectively, compared to PMAP-36. In addition, serum did not affect the antibacterial activity of RI18 against E. coli but inhibited the antifungal efficiency against C. albicans . Flow cytometry and electron microscopy observation revealed that RI18 killed microbial cells primarily by damaging membrane integrity, leading to whole cell lysis. Taken together, these results suggest that RI18 has potential for further therapeutic research against frequently-encountered bacteria and fungi. Meanwhile, modification of AMPs is a promising strategy for developing novel antimicrobials to overcome drug-resistance.

The metabolites produced by the gut microbiota are of interest to scientists. The objective of this review was to provide an updated summary of progress regarding the microbiota and their metabolites and influences on the pathogenesis of inflammatory bowel disease (IBD). The author retrieved information from the PubMed database up to January 2018, using various combinations of search terms, including IBD, microbiota, and metabolite. Both clinical studies and animal studies of intestinal microbiota and metabolites in IBD were selected. The information explaining the possible pathogenesis of microbiota in IBD was organized. In IBD patients, the biodiversity of feces/mucosa-associated microbiota is decreased, and the probiotic microbiota is also decreased, whereas the pathogenic microbiota are increased. The gut microbiota may be a target for diagnosis and treatment of IBD. Substantial amounts of data support the view that the microbiota and their metabolites play pivotal roles in IBD by affecting intestinal permeability and the immune response. This review highlights the advances in recent gut microbiota research and clarifies the importance of the gut microbiota in IBD pathogenesis. Future research is needed to study the function of altered bacterial community compositions and the roles of metabolites.

The permeability of thermally cracked granites is crucial information for understanding and modeling a number of processes in the earth’s crust, such as folding, geothermal activity, magmatic intrusions, and nuclear waste disposal. Factors, including the coefficient of thermal expansion, elastic modulus, grain size, and bonding stress, have a significant impact on thermal cracking and induced permeability. We performed thermal cracking experiments on granite with different grain sizes to determine the effect of grain size on permeability. The results indicated that permeability increased with temperature up to 700 °C for all samples. The ratio of permeability at the target temperature to that at room temperature is an exponential function of temperature. Coarse-grained granite has a higher increase in permeability than fine-grained granite. A mathematical model was presented to explain the effect of grain size on thermal cracking and induced permeability. In addition, the model can also quantitatively describe the influence of the linear thermal expansion coefficient and elastic modulus of minerals on thermal cracking.

Obstructive sleep apnea syndrome (OSAS) is a common breathing disorder in sleep in which the airways narrow or collapse during sleep, causing obstructive sleep apnea. The prevalence of OSAS continues to rise worldwide, particularly in middle-aged and elderly individuals. The mechanism of upper airway collapse is incompletely understood but is associated with several factors, including obesity, craniofacial changes, altered muscle function in the upper airway, pharyngeal neuropathy, and fluid shifts to the neck. The main characteristics of OSAS are recurrent pauses in respiration, which lead to intermittent hypoxia (IH) and hypercapnia, accompanied by blood oxygen desaturation and arousal during sleep, which sharply increases the risk of several diseases. This paper first briefly describes the epidemiology, incidence, and pathophysiological mechanisms of OSAS. Next, the alterations in relevant signaling pathways induced by IH are systematically reviewed and discussed. For example, IH can induce gut microbiota (GM) dysbiosis, impair the intestinal barrier, and alter intestinal metabolites. These mechanisms ultimately lead to secondary oxidative stress, systemic inflammation, and sympathetic activation. We then summarize the effects of IH on disease pathogenesis, including cardiocerebrovascular disorders, neurological disorders, metabolic diseases, cancer, reproductive disorders, and COVID-19. Finally, different therapeutic strategies for OSAS caused by different causes are proposed. Multidisciplinary approaches and shared decision-making are necessary for the successful treatment of OSAS in the future, but more randomized controlled trials are needed for further evaluation to define what treatments are best for specific OSAS patients.

Immune recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors often activates proinflammatory NF-κB signalling 1 . Recent studies indicate that the bacterial metabolite d -glycero-β- d -manno-heptose 1,7-bisphosphate (HBP) can activate NF-κB signalling in host cytosol 2 – 4 , but it is unclear whether HBP is a genuine PAMP and the cognate pattern recognition receptor has not been identified. Here we combined a transposon screen in Yersinia pseudotuberculosis with biochemical analyses and identified ADP-β- d -manno-heptose (ADP-Hep), which mediates type III secretion system-dependent NF-κB activation and cytokine expression. ADP-Hep, but not other heptose metabolites, could enter host cytosol to activate NF-κB. A CRISPR–Cas9 screen showed that activation of NF-κB by ADP-Hep involves an ALPK1 (alpha-kinase 1)–TIFA (TRAF-interacting protein with forkhead-associated domain) axis. ADP-Hep directly binds the N-terminal domain of ALPK1, stimulating its kinase domain to phosphorylate and activate TIFA. The crystal structure of the N-terminal domain of ALPK1 and ADP-Hep in complex revealed the atomic mechanism of this ligand–receptor recognition process. HBP was transformed by host adenylyltransferases into ADP-heptose 7-P, which could activate ALPK1 to a lesser extent than ADP-Hep. ADP-Hep (but not HBP) alone or during bacterial infection induced Alpk1 -dependent inflammation in mice. Our findings identify ALPK1 and ADP-Hep as a pattern recognition receptor and an effective immunomodulator, respectively. The bacterial metabolite ADP-heptose activates NF-κB in host cells via alpha-kinase 1 and the TIFA–TRAF signalling pathway.

Obstructive sleep apnea (OSA) drives immune dysregulation through its hallmark stressors—intermittent hypoxia (IH) and sleep fragmentation (SF). Beyond impaired sleep, OSA acts as a systemic inflammatory trigger that disrupts immune homeostasis and reshapes both innate and adaptive responses. Recent evidence shows that OSA activates hypoxia-inducible factor-1α (HIF-1α), NF-κB signaling, and the NLRP3 inflammasome, promoting chronic inflammation and immune-cell dysfunction. These alterations mechanistically contribute to OSA-associated cardiovascular disease, metabolic disorders, cognitive impairment, and tumor progression. Reframing OSA as an immune-modulating disorder highlights the need for diagnostics and therapies guided by immunology rather than airway management alone.

Aloperine (ALO) is an effective quinolizidine alkaloid. Previous research has demonstrated its antiarrhythmic effect by inhibiting voltage-gated sodium currents in rat ventricular myocytes. This study explored its effect on transient outward potassium currents (I ) in rat atrial myocytes to identify potential targets in the context of ion channel currents. The I characteristics in rat atrial myocytes were recorded using a whole-cell patch-clamp technique. Molecular docking was performed to validate ligand-protein binding interactions. ALO at concentrations of 3 and 10 μM significantly reduced I current densities. Gating kinetics analysis revealed ALO's ability to slow I activation, hasten inactivation, and prolong transition from inactive to resting state. Molecular docking revealed that ALO could stably bind to . ALO may inhibit I by slowing the activation process, accelerating inactivation, and delaying the recovery time after inactivation, potentially preventing acetylcholine-induced AF.

Background Bone mesenchymal stem cells (MSCs) can promote liver regeneration and inhibit inflammation and hepatic fibrosis. MSCs also can serve as a vehicle for gene therapy. Smad7 is an essential negative regulatory gene in the TGF-β1/Smad signalling pathway. Activation of TGF-β1/Smad signalling accelerates liver inflammation and fibrosis; we therefore hypothesized that MSCs overexpressing the Smad7 gene might be a new cell therapy approach for treating liver fibrosis via the inhibition of TGF-β1/Smad signalling. Methods MSCs were isolated from 6-week-old Wistar rats and transduced with the Smad7 gene using a lentivirus vector. Liver cirrhosis was induced by subcutaneous injection of carbon tetrachloride (CCl 4 ) for 8 weeks. The rats with established liver cirrhosis were treated with Smad7-MSCs by direct injection of cells into the main lobes of the liver. The expression of Smad7, Smad2/3 and fibrosis biomarkers or extracellular matrix proteins and histopathological change were assessed by quantitative PCR, ELISA and Western blotting and staining. Results The mRNA and protein level of Smad7 in the recipient liver and serum were increased after treating with Smad-MSCs for 7 and 21 days ( P  < 0.001). The serum levels of collagen I and III and collagenase I and III were significantly ( P  < 0.001) reduced after the treatment with Smad7-MSCs. The mRNA levels of TGF-β1, TGFBR1, α-SMA, TIMP-1, laminin and hyaluronic acid were decreased ( P  < 0.001), while MMP-1 increased ( P  < 0.001). The liver fibrosis score and liver function were significantly alleviated after the cell therapy. Conclusions The findings suggest that the MSC therapy with Smad7-MSCs is effective in the treatment of liver fibrosis in the CCl 4 -induced liver cirrhosis model. Inhibition of TGF-β1 signalling pathway by enhancement of Smad-7 expression could be a feasible cell therapy approach to mitigate liver cirrhosis.

Currently, the majority of antibiotics in clinical use have broad activity spectra, killing pathogenic and beneficial microorganisms indiscriminately. The disruption of the ecological balance of normal flora often results in secondary infections or other antibiotic-associated complications. Therefore, targeted antimicrobial therapies capable of specifically eliminating pathogenic bacteria while retaining the protective benefits of a normal microflora would be advantageous. In this study, we successfully constructed a series of Enterococcus faecalis -targeted antimicrobial peptides from wide-spectrum antimicrobial peptide precursors. These peptides are designed based on fusion of the species-specific peptide pheromone cCF10 and modification of the active region of the antimicrobial peptide. The results showed that cCF10-C4 possessed specific antimicrobial activity against E . faecalis and was not active against other types of bacteria tested. The specificity of this hybrid peptide was shown by the absence of antimicrobial effects in the pheromone-substituted derivative. Further studies indicated that cCF10-C4 and its parent peptide C4 exert their activities by damaging cytoplasmic membrane integrity. The present study reveals the application potential of these molecules as “probiotic” antimicrobials for the control of specific bacterial infections, and it also helps to elucidate the design and construction of species-specific antimicrobials with precise targeting specificity.