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In recent years, internet information technology has developed rapidly, and humanity has entered the information age. The rapid development of technology has led people to gradually pursue higher quality and more diversified education. The online teaching mode of the Internet enables the visualization of teaching resources, making online education further and more convenient. The innovative application of educational technology, represented by MOOCs and WeChat courses, has attracted industry attention, and online teaching and learning have become new trends in current learning.

With the increasing progress of the times and the rapid development of the Internet, in order to solve the actual needs of students, this online education platform project has been launched in combination with the teaching characteristics of various disciplines, aiming to improve the flexibility of teachers' teaching, enrich the learning channels of students, so as to use and learn at any time. This platform is based on ThinkPHP framework and MySQL database implementation to achieve the front-end separation.

With the goal of cultivating application-oriented and innovative talents, based on the teaching philosophy of "student-centered, output-oriented, continuous improvement", combined with modern information technology, and based on online and offline mixed teaching has become an inevitable trend of curriculum construction universities. This paper discusses the teaching reform research situation of “Network Application Development” course under the background of first-class Specialty, mixed teaching design, course teaching content and organization, course assessment and course evaluation, comprehensively exploring the new ideas of curriculum reform, and cultivating new engineering innovative talents.

Arginine is one of the host semiessential amino acids with diverse biological activities, and arginine depletion is associated with the incidence of many diseases. Arginine depletion induced by diet-derived interferon gamma (IFN-γ) leads to malignant transformation and impaired milk quality in healthy lactating bovine mammary epithelial cells (BMECs). However, the molecular mechanism of IFN-γ-induced arginine depletion is unclear. In this study, the BMEC cell line, mammary alveolar cells-large T antigen cells (MAC-T), was stimulated with IFN-γ (10 ng/mL) for 24 h, and cellular arginine and ornithine quantified by liquid chromatography-tandem mass spectrometry. Carnosine synthase 1 (

Neuronal PER-ARNT-SIM (PAS) domain protein 4 (NPAS4) is a protective transcriptional regulator whose dysfunction has been linked to a variety of neuropsychiatric and metabolic diseases. As a member of the basic helix–loop–helix PER-ARNT-SIM (bHLH-PAS) transcription factor family, NPAS4 is distinguished by an ability to form functional heterodimers with aryl hydrocarbon receptor nuclear translocator (ARNT) and ARNT2, both of which are also bHLH-PAS family members. Here, we describe the quaternary architectures of NPAS4-ARNT and NPAS4-ARNT2 heterodimers in complexes involving DNA response elements. Our crystallographic studies reveal a uniquely interconnected domain conformation for the NPAS4 protein itself, as well as its differentially configured heterodimeric arrangements with both ARNT and ARNT2. Notably, the PAS-A domains of ARNT and ARNT2 exhibit variable conformations within these two heterodimers. The ARNT PAS-A domain also forms a set of interfaces with the PAS-A and PAS-B domains of NPAS4, different from those previously noted in ARNT heterodimers formed with other class I bHLH-PAS family proteins. Our structural observations together with biochemical and cell-based interrogations of these NPAS4 heterodimers provide molecular glimpses of the NPAS4 protein architecture and extend the known repertoire of heterodimerization patterns within the bHLH-PAS family. The PAS-B domains of NPAS4, ARNT, and ARNT2 all contain ligand-accessible pockets with appropriate volumes required for small-molecule binding. Given NPAS4’s linkage to human diseases, the direct visualization of these PAS domains and the further understanding of their relative positioning and interconnections within the NPAS4-ARNT and NPAS4-ARNT2 heterodimers may provide a road map for therapeutic discovery targeting these complexes.

Background Amyloid β (Aβ) is a hallmark of Alzheimer’s disease (AD). Insufficient sleep duration and poor sleep quality have been found to be a risk factor of developing AD because sleep may involve regulating Aβ. However, the magnitude of the relationship between sleep duration and Aβ is still unclear. This systematic review examines the relationship between sleep duration and Aβ in later-life adults.Methods We screened 5,005 published articles searched from relevant electronic databases (i.e., PubMed, CINAHL, Embase, and PsycINFO) and reviewed 14 articles for the qualitative synthesis and 7 articles for the quantitative synthesis.Results Mean ages of the samples ranged from 63 to 76. Studies measured Aβ using cerebrospinal fluid, serum, and positron emission tomography scans with two tracers: Carbone 11-labeled Pittsburgh compound B or fluorine 18–labeled. Sleep duration was subjectively measured using interviews, questionnaires, or using objective measures such as polysomnography or actigraphy. The studies accounted for demographic and lifestyle factors in their analyses. Five of the 14 studies reported a statistically significant association between sleep duration and Aβ. Using seven eligible articles, our quantitative synthesis demonstrated that the average association between sleep duration and Aβ was not statistically significant (Fisher’s Z = -0.006, 95% CI= -0.065 ~ 0.054).Conclusion This review suggests that caution should be taken when considering sleep duration as the primary factor for Aβ levels. More studies are needed using a longitudinal design, comprehensive sleep metrics, and larger sample sizes to advance our understanding of the optimal sleep duration and AD prevention.

Genus Rickettsia associated to blood-feeding arthropods are usually pathogenic when transmitted to vertebrates. These species include the agents of acute human disease such as typhus and Rocky Mountain spotted fever. However, many other Rickettsia have been uncovered with uncertain pathogenic to vertebrates in recent surveys. It is therefore perhaps more appropriate to consider these Rickettsiaas endosymbionts that are transmitted vertically in invertebrates, and secondarily as pathogens of vertebrates. Rickettsia canadensis, an ancestor species in genus Rickettsia, had been well characterized for its peculiar genome size and genes’ contents bridging the pathogenic Rickettsiaand non-pathogenic ones. However, there is few research on the ancient rickettsia species in China which may seriously influence our pursue for the evolutionary nature of Rickettsia in China. In the present study, R. canadensis was detected from Ixodes persulcatusticks from forest areas of both Heilongjiang province and Inner Mongolia Autonomous Region in northern China. The molecular evidences from both 16S rRNA gene and 3 arrays of gene transcripts strongly indicated the natural infection of R. canadensis occurs in Ixodid ticks in China. The gene transcripts including rpoB-rpoC-rpoC/160KDa-leucyl aminopeptidase-hypothetical protein-leucyl aminopeptidase-aspartate tRNA ligase, RlmE-Omp 1-Peptidase M50-nusB, dnaK-dnaJ-ChaBfamily protein-BamD-RecN-Carboxypeptidase M32 revealed from I. persulcatus suggested the intensive interactions between R. canadensis and. host ticks, which would provide scientific clues to highlight the possible evolutionary trajectory of Rickettsia species in China.

Bi2WO6/TiO2 heterostructure was obtained by a simple way. The crystal form and elemental composition of Bi2WO6/TiO2 photocatalyst were characterized by XRD, UV-vis, SEM, TEM, EDS as well as XPS. The synthesized heterojunction has a wide absorption in the visible light area, which provides a good basis for the photocatalytic degradation of organic dye applications. The photocatalytic performance and pollutant degradation efficiency of Bi2WO6/TiO2 photocatalyst were studied. The photocatalytic degradation activity of Bi2WO6/TiO2 is stronger than Bi2WO6 and TiO2. The degradation of Bi2WO6/TiO2 photocatalyst to Methylene blue (MB) was investigated under visible light irradiation. According to the energy band position, the result of photoluminescence (PL) and the capture experiment of active species, a mechanism to significantly improve the photocatalytic performance is proposed. In addition, the photocatalyst not only has good photocatalytic performance but also has good stability.

Dairy cow mastitis is a common bacterial infectious disease which seriously threatens the development of the dairy cow industry. Previous studies have found that increased IFN-γ expression in dairy cows makes dairy cows more susceptible to mastitis, but the underlying mechanism is still not known. In this study, we utilized the in vitro bovine mammary epithelial cells (BMECs) model to explore the molecular mechanism via transcriptome sequencing technology, immunofluorescence, and Western blotting. It was found that IFN-γ promoted the adhesion and invasion of Staphylococcus aureus to BMECs through increasing the expression of TLR4-mediated CCL5 in BMECs. IFN-γ increased the activity of arginase II and reduced the level of arginine in cells, while the addition of arginine inhibited the expression of TLR4 and CCL5. An invasion experiment in mice further validated that IFN-γ treatment significantly increased the bacterial load in mammary glands and blood. However, the colonization and diffusion of S. aureus were interestingly decreased after Arg supplement. These data reveal that increased IFN-γ reduces arginine levels and activates TLR4-CCL5 signaling, leading to enhanced susceptibility of BMECs to S. aureus. Our findings are helpful to understand the pathogenesis of dairy cow mastitis and provide a theoretical basis for improvement of mastitis resistance in dairy cows.

Monitoring crop development and accurately estimating crop yield are important to improve field management and crop production. This study aimed to evaluate the performance of an unmanned aerial vehicle (UAV)-based remote sensing system in cotton yield estimation. A UAV system, equipped with an RGB camera, a multispectral camera, and an infrared thermal camera, was used to acquire images of a cotton field at two growth stages (flowering growth stage and shortly before harvest). Sequential images from the three cameras were processed to generate orthomosaic images and a digital surface model (DSM), which were registered to the georeferenced yield data acquired by a yield monitor mounted on a harvester. Eight image features were extracted, including normalised difference vegetation index (NDVI), green normalised difference vegetation index (GNDVI), triangular greenness index (TGI), a channel in CIE-LAB colour space (a∗), canopy cover, plant height (PH), canopy temperature, and cotton fibre index (CFI). Models were developed to evaluate the accuracy of each image feature for yield estimation. Results show that PH and CFI were the best single features for cotton yield estimation, both with R2 = 0.90. The combination of PH and CFI, PH and a∗, or PH and temperature were the best two-feature models with R2 from 0.92 to 0.94. The best three-feature models were among the combinations of PH, CFI, temperature and a∗. This study found that UAV-based images collected during the flowering growth stage and/or shortly before harvest were able to estimate cotton yield accurately.

Infections induced by fungi, especially the drug-resistant fungi, are difficult clinical problems. Conventional antifungal treatment is effective but due to resistance, treatment failure, and treatment-related toxicity, there is a need for new antifungal drugs. In this study, SA-2 (YYRRLLRVLRRRW) was derived from Cystatin-SA, a saliva protein with a molecular weight of 14 kDa. Meanwhile, the structure-activity of SA-2 and its mutants was also studied. We detected the antimicrobial activity and cytotoxicity of SA-2 and found that SA-2 had a low cytotoxicity toward mammalian cells but a good inhibitory effect on Candida albicans (C. albicans) and Cryptococcus neoformans (C. neoformans), with MIC values of 16-64 μg/mL and 8-32 μg/mL, respectively. Interestingly, SA-2 effectively killed fluconazole-resistant C. neoformans and C. albicans within 12 h. This antifungal activity against fluconazole-resistant fungi was comparable to that of amphotericin B. In addition, the C. neoformans-infected mice model was established to evaluate the anti-infective activity of SA-2 in vivo. Results showed that SA-2 significantly reduced the counts of fungi in lung and brain tissues to protect fluconazole-resistant C. neoformans-infected mice from death without changing mice body weights. Moreover, the dramatically increased pro-inflammatory cytokines TNF-α, IL-6 and IL-1β induced by intranasal infection of C. neoformans could be obviously declined due to the treatment of SA-2, which may be attributed to the elimination of C. neoformans in time in the infected tissue. For the mode of actions underlying SA-2 against C. neoformans, we found that the cationic peptide SA-2 could adhere to the negatively charged fungal cell membrane to increase the surface potential of C. neoformans in a dose-dependent manner, and finally disrupted the integrity of fungal cell membrane, reflecting as a 60% positive rate of propidium iodide uptake of C. neoformans cells after SA-2 (4 × MIC) treatment. Our study indicated that SA-2 has the potential to develop as a new therapeutic agent against infection induced by drug-resistant fungi.

Background Few studies to date have evaluated the use of Lactobacillus and Bifidobacterium in edible fungus fermentation. To obtain a fermented Lentinus edodes (L. edodes) liquid product with good taste and effects, a strain with good fermentation performance from 9 tested strains was selected, and the physicochemical properties and antioxidant capacity of the resulting product were evaluated. Results Lactobacillus fermentum 21828 exhibited adhesion, tolerance to low pH and bile salts, and good fermentation performance. The number of viable bacteria was 1.05×108 CFU mL -1 , and the extraction rate of crude polysaccharide from L. edodes was 2.79% after fermentation. The effects of fermentation on the contents and composition of nutrients in L. edodes liquid were marked, with changes in total soluble protein, total soluble sugar, total acid, and total phenol levels. The DPPH (2,2-diphenyl-1-picrylhydrazyl) radical-scavenging rate in the fermentation liquid was 93.01%, which was significantly higher than that in non-fermented liquid (80.33%). Furthermore, analysis of volatile and 5'-nucleotide contents showed that fermentation altered the flavor of the product, whereas sensory evaluation showed that the fermented product was preferred. Conclusion Our study demonstrated that the fermented Lentinus edodes liquid exhibited better nutritional and functional properties as well as sensory characteristics, compared to unfermented. This article is protected by copyright. All rights reserved.

Hypoxia-inducible factors (HIFs) are α/β heterodimeric transcription factors modulating cellular responses to the low oxygen condition. Among three HIF-α isoforms, HIF-3α is the least studied to date. Here we show that oleoylethanolamide (OEA), a physiological lipid known to regulate food intake and metabolism, binds selectively to HIF-3α. Through crystallographic analysis of HIF-3 α/β heterodimer in both apo and OEA-bound forms, hydrogen-deuterium exchange mass spectrometry (HDX-MS), molecular dynamics (MD) simulations, and biochemical and cell-based assays, we unveil the molecular mechanism of OEA entry and binding to the PAS-B pocket of HIF-3α, and show that it leads to enhanced heterodimer stability and functional modulation of HIF-3. The identification of HIF-3α as a selective lipid sensor is consistent with recent human genetic findings linking HIF-3α with obesity, and demonstrates that endogenous metabolites can directly interact with HIF-α proteins to modulate their activities, potentially as a regulatory mechanism supplementary to the well-known oxygen-dependent HIF-α hydroxylation.

In this paper, we study blow up and blow up time of solutions for initial boundary value problem of Kirchhoff-type wave equations involving the fractional Laplacian \begin{document}$\left\{ \begin{align} & {{u}_{tt}}+[u]_{s}^{2(\theta -1)}{{(-\Delta )}^{s}}u=f(u),\ \ \ \ \text{in}\ \Omega \times {{\mathbb{R}}^{+}}, \\ & u(x,0)={{u}_{0}},\ \ {{u}_{t}}(x,0)={{u}_{1}},\ \ \ \ \ \ \text{in}\ \Omega , \\ & u=0,\ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \text{in}\ ({{\mathbb{R}}^{N}}\backslash \Omega )\times \mathbb{R}_{0}^{+}, \\ \end{align} \right.$\end{document} where \begin{document}$ [u]_s $\end{document} is the Gagliardo seminorm of \begin{document}$ u $\end{document} , \begin{document}$ s\in(0, 1) $\end{document} , \begin{document}$ \theta\in[1, 2_s^*/2) $\end{document} with \begin{document}$ 2_s^* = \frac{2N}{N-2s} $\end{document} , \begin{document}$ (-\Delta)^s $\end{document} is the fractional Laplacian operator, \begin{document}$ f(u) $\end{document} is a differential function satisfying certain assumptions, \begin{document}$ \Omega\subset\mathbb{R}^N $\end{document} is a bounded domain with Lipschitz boundary \begin{document}$ \partial \Omega $\end{document} . By introducing a new auxiliary function and an adapted concavity method, we establish some sufficient conditions on initial data such that the solutions blow up in finite time for the arbitrary positive initial energy. Moreover, as \begin{document}$ f(u) = |u|^{p-1}u $\end{document} , we estimate the upper and lower bounds for blow up time with arbitrary positive energy.

Accurate crop yield estimation is important for agronomic and economic decision-making. This study evaluated the performance of imagery data acquired using a unmanned aerial vehicle (UAV)-based imaging system for estimating yield of maize (Zea mays L.) and the effects of variable-rate nitrogen (N) application on crops. Images of a 27-ha maize field were captured using a UAV with a consumer-grade RGB camera flying at ~100 m above ground level at three maize growth stages. The collected sequential images were stitched and the Excess Green (ExG) colour feature was extracted to develop prediction models for maize yield and to examine the effect of the variable-rate N application. Various linear regression models between ExG and maize yield were developed for three sample area sizes (21, 106, and 1058 m2). The model performance was evaluated using coefficient of determination (R2), F-test and the mean absolute percentage error (MAPE) between estimated and actual yield. All linear regression models between ExG and yield were significant (p ≤ 0.05). The MAPE ranged from 6.2 to 15.1% at the three sample sizes, although R2 values were all

Apples are rich in phenolic antioxidants, which have various beneficial effects on human health. The purposes of our study were to evaluate the effects of Lactobacillus fermentum 21828 fermentation on the phytochemical composition and bioactivity of Aksu (Fuji) apple juice (AJ), and to evaluate the hypoglycemic effect of fermented AJ (FAJ) and its effect on intestinal flora. Fermentation altered the phytochemistry and enhanced the biological activity (hypoglycemic and antioxidant activities) of AJ. FAJ improved fasting blood glucose and insulin levels in diabetic mice, regulated blood lipid metabolism, reduced oxidative damage, restored damaged islet cells, and reshaped the intestinal flora of diabetic mice by increasing the relative abundance of Actinobacteria, Bifidobacteria, and Faecalibaculum. The results indicate that FAJ is a fermented product that is rich in bioactive components and has potential hypoglycemic and antioxidant activities.

Alzheimer's disease (AD) commonly involves neuropsychiatric symptoms (NPS), such as nighttime behaviors (or sleep disturbance), hallucination, delusion, or mood changes. However, it is unclear how NPS and sleep disturbances are correlated with AD biomarkers. The purpose of this analysis was to examine how NPS and nighttime behaviors are associated with AD CSF biomarkers by cognitive status. A total of 1,667 subjects’ (mean age = 69.4 SD=9.3, 48 % (808) were male) data from the National Alzheimer’s Disease Coordinating Center (NACC) were used, including subjects with dementia (n = 577), mild cognitive impairment (MCI, n = 363), cognitive impairment but not MCI (n = 47), cognitive impairment due to Alzheimer’s etiology (n= 608), and normal cognition (n = 680). The nighttime symptoms, number, and severity of NPS were assessed using the Neuropsychiatric Inventory Questionnaire Quick Version (NPI-Q). Cerebrospinal fluid (CSF) samples were analyzed for Aβ42,dft5 t-tau, p-tau. We used generalized linear models to explore the associations accounting for age, sex, APOE4 alleles, and BMI. We found the number of NPS were associated with Aβ42 (p = 0.042) in individuals with MCI, impaired, or dementia due to Alzheimer’s etiology. Yet, the number of NPS were not associated with t-tau or p-tau in individuals with and without dementia. The severity of NPS including nighttime symptoms were not associated with biomarkers. Our results could suggest that the number of NPS can be reflected by higher CSF Aβ42 levels in the individuals with Alzheimer’s etiology. Future longitudinal analyses are warranted to understand the causal relationships.

It makes sense to use environmentally friendly methods of degreasing in fur-making process. In this study, subcritical n-pentane was used to degrease wool fibers. Thermogravimetric analysis (TGA) was used to observe and analyze the properties of the subcritical n-pentane degreased wool fibers. The results showed that the thermal stability of the fibers increased. Fourier Transform Infrared (FTIR) spectroscopy was used to analyze the structural changes of macromolecular chains in wool fibers. It was found that when the pressure was higher than 0.4 MPa, the wool fibers underwent a conformational change with the α-helix changing to β-folding. If the pressure was as high as 0.6 MPa, the disulfide bonds in the wool fibers scale layer appeared to break. X-ray powder diffraction experiment was used to study changes in wool fiber aggregation morphology. It was demonstrated that the crystalline zone of wool fibers changed and the fibers index grew, from 22.89% to 30.19%. Field emission scanning electron microscopy and ultra-depth of field microscopy was used to analyze changes in the surface morphology of wool fibers. The results suggested that after the treatment, the wool fibers were not damaged and the impurities on the wool surface were reduced.

Obesity and hyperglycemia are two serious chronic diseases that are increasing in incidence worldwide. This research aimed to develop a fermented cloudy apple juice with good hyperglycemia intervention activities. Here, cloudy apple juice (CAJ), cloudy apple juice rich in polyphenols (CAJP) and fermented cloudy apple juice rich in polyphenols (FCAJP) were prepared sequentially, and then the effects of the three apple juices on weight, lipid level, gut microbiota composition and intestinal tract health were evaluated for obese mice induced by a high-fat diet. The research findings revealed that the FCAJP showed potential to inhibit the weight gain of mice, reduce fat accumulation, and regulate the blood lipid levels of obese mice by decreasing the ratio of the Firmicutes/Bacteroidotas, improving the Sobs, Ace, and Chao indexes of the gut microbiota and protecting intestinal tract health. In addition, the FCAJP augmented the abundance of Akkermansia and Bacteroides, which were positively related to SCFAs in cecal contents. This study inferred that FCAJP could be developed as a healthy food for preventing obesity and hyperglycemia.

Degreasing is one of the important processes for the production of leather and fur. This study aimed to develop a degreasing method using subcritical n-pentane. Sheep skin was chosen as raw skin for this investigation. The best possible combination of degreasing parameters was found using single factor experiment and response surface methodology. The effects of temperature and pressure on the degreasing efficiency were evaluated further with histological analysis. The results showed that the optimum degreasing parameters were a degreasing time of 58 min, pressure of 0.45 MPa, temperature of 41.0°C and thus yielded a degreasing rate of 52.46％ theoretically and 51.46% experimentally. Histological sections showed that the degreasing effect of subcritical n-pentane was quite significant and the lipid droplets around the hair follicles were dramatically reduced. It has been proven that subcritical n-pentane degreasing is an effective technique for sheep skin degreasing.

To improve flight economy and environmental friendliness, a vertical flight profile optimization method considering the cost of pollutant emissions (SO 2 , CO, NO x , CO 2 and HC) cost is studied. Firstly, in this paper, a pollutant emission price weight, emission factor and a comprehensive cost index are proposed to establish a direct operating costs calculation model considering the pollutant emissions cost based on the ICAO baseline emission data. Secondly, based on the energy state method and the mass-point dynamics, a mass-point dynamic model of the vertical flight profile is established. Thirdly, the objective function and constraint conditions of trajectory optimization in each flight phase are derived based on the minimum principle of Pontryagin. Finally, taking B737-800 as an example, the Particle Swarm Optimization (PSO) algorithm is used to optimize the objective functions as well as fight parameters under a proper comprehensive cost index, and through simulation to realize the trajectory optimization with the optimal cost as the goal. Under the same conditions, compared the optimization result with the traditional cost index of 30, the fuel cost is reduced by 4.2%, total emissions of pollutants decreased by 4.3%, flight time increased by 7.9%, but the total cost of flight decreased by 2.1%. The simulation results show that the vertical profile trajectory optimization method proposed in this paper can effectively reduce the emissions of SO 2 , HC, CO, NO x , CO 2 and the direct operating costs, improving the flight economic efficiency for airlines.

Rare earth (RE) complexes have found a variety of applications in materials science and biomedicine because of their unique luminescence properties. However, the poor stability and solubility in water of multicomponent RE assemblies significantly limit their practical applications. We rationally designed and developed a novel Eu

Gut microbiota (GM) modifies the intrahepatic immune microenvironment, but the underlying mechanisms remain poorly understood. Liver fibrosis-associated imprinting is predicted to be reflected in GM. This study investigated the link between GM and the intrahepatic T cell receptor (TCR) immune repertoire (IR), and whether GM modulates the intrahepatic immune microenvironment via TCR IR during liver fibrosis. We analyzed the correlation between GM and TCR IR during liver fibrogenesis. Accordingly, 16S rRNA gene sequencing (16S-seq) and bulk immune repertoire sequencing (IR-seq) were performed to characterize GM and intrahepatic TCR IR. Fecal microbial transplant (FMT) and TCRβ knockout (TcrbKO) mouse models were employed to determine the biological link between GM and TCR IR in liver fibrosis. We found that GM and intrahepatic TCR IR are highly correlated, with both showing reduced diversity and centralized distribution during liver fibrosis. The restoration of normal intestinal microbiota may reshape intrahepatic TCR IR and delay liver fibrosis. Interestingly, TCR IR ablation abrogated the impact of GM on liver fibrogenesis. Furthermore, GM modulated hepatic stellate cell (HSC) activation via TCR IR-mediated intrahepatic immune milieu. Our study demonstrates that GM, which exhibits cross-talk with the intrahepatic TCR IR, influences the intrahepatic immune microenvironment and liver fibrosis progression.