A Stapled Peptide Inhibitor Targeting the Binding Interface of N6-Adenosine-Methyltransferase Subunits METTL3 and METTL14 for Cancer Therapy.

METTL3, a primary methyltransferase catalyzing the RNA N6-methyladenosine (m6A) modification, has been identified as an oncogene in several cancer types and thus nominated as a potentially effective target for therapeutic inhibition. However, current options using this strategy are limited. In this study, we targeted protein-protein interactions at the METTL3-METTL14 binding interface to inhibit complex formation and subsequent catalysis of the RNA m6A modification. Among candidate peptides, RM3 exhibited the highest anti-cancer potency, inhibiting METTL3 activity while also facilitating its proteasomal degradation. We then designed a stapled peptide inhibitor (RSM3) with enhanced peptide stability and formation of the α-helical secondary structure required for METTL3 interaction. Functional and transcriptomic analysis in vivo indicated that RSM3 induced upregulation of programmed cell death-related genes while inhibiting cancer-promoting signals. Furthermore, tumor growth was significantly suppressed while apoptosis was enhanced upon RSM3 treatment, accompanied by increased METTL3 degradation, and reduced global RNA methylation levels in two in vivo tumor models. This peptide inhibitor thus exploits a mechanism distinct from other small-molecule competitive inhibitors to inhibit oncogenic METTL3 activity. Our findings collectively highlight the potential of targeting METTL3 in cancer therapies through peptide-based inhibition of complex formation and proteolytic degradation.

Aflibercept Loaded Eye-Drop Hydrogel Mediated with Cell-Penetrating Peptide for Corneal Neovascularization Treatment.

Corneal neovascularization (CoNV) is a major cause of visual impairment worldwide. Currently, available treatment options have limited efficacy and are associated with adverse effects due to biological barriers and clearance mechanisms. To address this challenge, a novel topical delivery system is developed-Gel 2_1&Eylea-an aflibercept-loaded eye-drop hydrogel mediated with cell-penetrating peptide 1. Gel 2_1&Eylea demonstrates superior membrane permeability, increased stability, and prolonged drug retention time on the ocular surface, and thus may improve drug efficacy. In a rabbit CoNV model, Gel 2_1&Eylea significantly reduces the density of neovascularization with no adverse effects on normal corneoscleral limbal vessels, demonstrating high efficacy and biocompatibility. This work identifies a promising treatment for CoNV which has the potential to benefit other ocular neovascular diseases.

Computed tomography angiography-based radiomics model to identify high-risk carotid plaques.

Background: Extracranial atherosclerosis is one of the major causes of stroke. Carotid computed tomography angiography (CTA) is a widely used imaging modality that allows detailed assessments of plaque characteristics. This study aimed to develop and test radiomics models of carotid plaques and perivascular adipose tissue (PVAT) to distinguish symptomatic from asymptomatic plaques and compare the diagnostic value between radiomics models and traditional CTA model. Methods: A total of 144 patients with carotid plaques were divided into symptomatic and asymptomatic groups. The traditional CTA model was built by the traditional radiological features of carotid plaques measured on CTA images which were screened by univariate analysis and multivariable logistic regression. We extracted and screened radiomics features from carotid plaques and PVAT. Then, a support vector machine was used for building plaque and PVAT radiomics models, as well as a combined model using traditional CTA features and radiomics features. The diagnostic value between radiomics models and traditional CTA model was compared in identifying symptomatic carotid plaques by Delong method. Results: The area under curve (AUC) values of traditional CTA model were 0.624 and 0.624 for the training and validation groups, respectively. The plaque radiomics model and PVAT radiomics model achieved AUC values of 0.766, 0.740 and 0.759, 0.618 in the two groups, respectively. Meanwhile, the combined model of plaque and PVAT radiomics features and traditional CTA features had AUC values of 0.883 and 0.840 for the training and validation groups, respectively, and the receiver operating characteristic curves of combined model were significantly better than those of traditional CTA model in the training group (P<0.001) and validation group (P=0.029). Conclusions: The combined model of the radiomics features of carotid plaques and PVAT and the traditional CTA features significantly contributes to identifying high-risk carotid plaques compared with traditional CTA model.

Early assessment of acute kidney injury in severe acute pancreatitis with multimodal DWI: an animal model.

OBJECTIVES: To evaluate the feasibility of multimodal diffusion-weighted imaging (DWI) for detecting the occurrence and severity of acute kidney injury (AKI) caused by severe acute pancreatitis (SAP) in rats. METHODS: SAP was induced in thirty rats by the retrograde injection of 5.0% sodium taurocholate through the biliopancreatic duct. Six rats underwent MRI of the kidneys 24 h before and 2, 4, 6, and 8 h after this AKI model was generated. Conventional and functional MRI sequences were used, including intravoxel incoherent motion imaging (IVIM), diffusion tensor imaging (DTI), and diffusion kurtosis imaging (DTI). The main DWI parameters and histological results were analyzed. RESULTS: The fast apparent diffusion coefficient (ADC) of the renal cortex was significantly reduced at 2 h, as was the fractional anisotropy (FA) value of the renal cortex on DTI. The mean kurtosis (MK) values for the renal cortex and medulla gradually increased after model generation. The renal histopathological score was negatively correlated with the medullary slow ADC, fast ADC, and perfusion scores for both the renal cortex and medulla, as were the ADC and FA values of the renal medulla in DTI, whereas the MK values of the cortex and medulla were positively correlated (r = 0.733, 0.812). Thus, the cortical fast ADC, medullary MK, FADTI, and slow ADC were optimal parameters for diagnosing AKI. Of these parameters, cortical fast ADC had the highest diagnostic efficacy (AUC = 0.950). CONCLUSIONS: The fast ADC of the renal cortex is the core indicator of early AKI, and the medullary MK value might serve as a sensitive biomarker for grading renal injury in SAP rats. CLINICAL RELEVANCE STATEMENT: The multimodal parameters of renal IVIM, DTI, and DKI are potential beneficial for the early diagnosis and severity grading of renal injury in SAP patients. KEY POINTS: • The multimodal parameters of renal DWI, including IVIM, DTI, and DKI, may be valuable for the noninvasive detection of early AKI and the severity grading of renal injury in SAP rats. • Cortical fast ADC, medullary MK, FA, and slow ADC are optimal parameters for early diagnosis of AKI, and cortical fast ADC has the highest diagnostic efficacy. • Medullary fast ADC, MK, and FA as well as cortical MK are useful for predicting the severity grade of AKI, and the renal medullary MK value exhibits the strongest correlation with pathological scores.

Comparison of the imaging and clinical characteristics between Initial and Recurrent Alcoholic Acute Pancreatitis: a retrospective cross-sectional study.

MATERIALS: Patients with alcoholic acute pancreatitis in our hospital were recruited from Jan 2019 to July 2022 and divided into IAAP and RAAP groups. All patients underwent Contrast-Enhanced Computerized Tomography (CECT) or Magnetic Resonance Imaging (MRI) after administration. Imaging manifestations, local complications, severity scores on the Modified CT/MR Severity Index (MCTSI/MMRSI), Extrapancreatic Inflammation on CT/MR (EPIC/M), clinical severity [Bedside Index for Severity in Acute Pancreatitis (BISAP) Acute Physiology and Chronic Health Evaluation (APACHE-II)], and clinical prognosis were compared between the two groups.Results: 166 patients were recruited for this study, including 134 IAAP (male sex 94%) and 32 RAAP patients (male sex 100%). On CECT or MRI, IAAP patients were more likely to develop ascites and Acute Necrosis collection (ANC) than RAAP patients (ascites:87.3%vs56.2%; P = .01; ANC:38%vs18.7%; P < .05). MCTSI/MMRSI and EPIC/M scores were higher in IAAP than in RAAP patients(MCTSI/MMRSI:6.2vs5.2; P < .05; EPIC/M:5.4vs3.8; P < .05).Clinical severity scores (APACHE-II and BISAP), length of stay, and systemic complications [Systemic Inflammatory Response Syndrome (SIRS), respiratory failure] were higher in the IAAP group than in the RAAP group (P < .05). No mortality outcomes were reported in either group while hospitalized.Conclusions: Patients with IAAP had more severe disease than those with RAAP. These results may be helpful for differentiating care paths for IAAP and RAAP, which are essential for management and timely treatment in clinical practice.

Low crosstalk trapezoid-index thirteen-core single-mode fiber for multi-channel and high-density applications.

Multi-core fiber based on space division multiplexing technology provides a practical solution to achieve multi-channel and high-capacity signal transmission. However, long-distance and error-free transmission remains challenging due to the presence of inter-core crosstalk within the multi-core fiber. Here, we propose and prepare a novel trapezoid-index thirteen-core single-mode fiber to solve the problems that MCF has large inter-core crosstalk and the transmission capacity of single-mode fiber approaches the upper limit. The optical properties of thirteen-core single-mode fiber are measured and characterized by experimental setups. The inter-core crosstalk of the thirteen-core single-mode fiber is less than -62.50 dB/km at 1550 nm. At the same time, each core can transmit signals at a data rate of 10 Gb/s and achieve error-free signal transmission. The prepared optical fiber with a trapezoid-index core provides a new and feasible solution for reducing inter-core crosstalk, which can be loaded into current communication systems and applied in large data centers.

Experimental research of 13-core 5-LP mode fiber with high doped graded-index core and stairway-index trench.

A graded-index 13-core 5-LP mode fiber with high doped core and stairway-index trench structure have been successfully prepared by Hole-drilling method and Plasma vapor deposition. This fiber has 104 spatial channels, realizing large capacity information transmission. By building an experimental platform, the 13-core 5-LP mode fiber have been tested and characterized. The core can stably transmit 5 LP modes. The transmission loss is lower than 0.5 dB/km. Inter-core crosstalk (ICXT) of each layer of core is analyzed in detail. The ICXT can be less than -30 dB/100 km. The test results show that this fiber can stably transmit 5 LP modes, and has the characteristics of low loss and low crosstalk, realizing large capacity transmission. This fiber provides a solution to the issue of limited fiber capacity.

Weakly coupled graded index heterogeneous nineteen-core few-mode fiber.

We propose a novel heterogeneous nineteen-core four-mode fiber. The heterogeneous core arrangement and trench-assisted structure can significantly suppress inter-core crosstalk (XT). In order to control the number of modes in the core, a low refractive index area is introduced in the core. The number of LP modes and the effective refractive index difference (Δneff) of adjacent modes in the core are controlled by changing the refractive index distribution of the core and the parameters of the low refractive index area in the core. And the mode state of low intra-core crosstalk is successfully realized in the graded index core. After the optimization of fiber parameters, each core can stably transmit four LP modes under the optimal fiber parameters, and the inter-core crosstalk of LP02 mode is less than -60 dB/km. Finally, the effective mode area (Aeff) and dispersion (D) of nineteen-core four-mode fiber in C+L band are described. The results show that the nineteen-core four-mode fiber is suitable for terrestrial and undersea communication systems, data centers, optical sensors and other fields.

Predictive Value of the Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Monocyte-to-Lymphocyte Ratio Esophageal Stricture After Endoscopic Submucosal Dissection of Early Esophageal Cancer.

BACKGROUND Endoscopic submucosal dissection (ESD) has become a preferred treatment method for patients with early esophageal cancer (EEC), but it can easily be complicated by esophageal stricture. In this study, we aimed to analyze the predictive value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) for post-ESD esophageal stricture of EEC. MATERIAL AND METHODS A retrospective study of 285 patients with EEC who underwent ESD was conducted. Patients were divided into 2 groups according to whether there were complications of esophageal stricture: the stricture group (n=72) and the non-stricture group (n=213). A t test or chi-squared test was used to compare the clinical differences in different subgroups. Receiver operating characteristic (ROC) curves were plotted to determine and compare the predictive value of NLR, PLR, and MLR in post-ESD esophageal stricture. Spearman correlation was used to detect the relationship between NLR, PLR, and MLR and the severity of esophageal stricture. RESULTS The NLR, PLR, and MLR values in the stricture group were higher than those in the non-stricture group, and there was a positive correlation between NLR and MLR and the severity of stricture according to the Spearman correlation test (P<0.05). ROC analysis showed that the area under the ROC curve value of the combination of NLR, PLR, and MLR (0.850) was higher than the NLR (0.792), PLR (0.774), and MLR (0.768). CONCLUSIONS The combination of NLR, PLR, and MLR could help clinicians to predict post-ESD esophageal stricture in the early stage.

Air-Stable Organoradical Boron Reagents.

Both organic radicals and organoboron reagents have been broadly investigated, but the combination of them via direct C-H borylation as organic radical building blocks has never been achieved. Herein, a series of organoradical boron reagents, such as TTM-Bpin and TTM-BOH, were synthesized through the key step of C-H borylation of substrate TTM-H ((2,6-dichlorophenyl) bis(2,4,6-trichlorophenyl)methyl) radical for the first time. They are air stable enough to be stored in the solid state for several months under dark conditions, and fully investigated through single crystal analysis, EPR and DFT calculations. Furthermore, they can smoothly work in the standard Suzuki-Miyaura coupling (SMC) reaction with retention of the carbon radical center. Meanwhile, these radical species bearing different boron units display fluorescent character and are potentially applied for the collective synthesis of luminescent organic radicals, as well as other functionalized open-shell materials.

MC1R Peptide Agonist Self-Assembles into a Hydrogel That Promotes Skin Pigmentation for Treating Vitiligo.

Vitiligo, a common skin disease that seriously affects 0.5-2.0% of the worldwide population, lacks approved therapeutics due to a wide range of adverse side effects. As a key regulator of skin pigmentation, MC1R may be an effective therapeutic target for vitiligo. Herein, we report an MC1R peptide agonist that directly self-assembles into nanofibrils that form a hydrogel matrix under normal physiological conditions. This hydrogel exhibits higher stability than free peptides, sustained release, rapid recovery from shear-thinning, and resistance to enzymatic proteolysis. Furthermore, this peptidal MC1R agonist upregulates tyrosinase, tyrosinase-related protein-1 (TYRP-1), and tyrosinase-related protein-2 (TYRP-2) to stimulate melanin synthesis. More importantly, MC1R agonist hydrogel promotes skin pigmentation in mice more potently than free MC1R agonist. This study supports the development of this MC1R agonist hydrogel as a promising pharmacological intervention for vitiligo.

Antagonizing apolipoprotein J chaperone promotes proteasomal degradation of mTOR and relieves hepatic lipid deposition.

BACKGROUND AND AIMS: Overnutrition-induced activation of mammalian target of rapamycin (mTOR) dysregulates intracellular lipid metabolism and contributes to hepatic lipid deposition. Apolipoprotein J (ApoJ) is a molecular chaperone and participates in pathogen-induced and nutrient-induced lipid accumulation. This study investigates the mechanism of ApoJ-regulated ubiquitin-proteasomal degradation of mTOR, and a proof-of-concept ApoJ antagonist peptide is proposed to relieve hepatic steatosis. APPROACH AND RESULTS: By using omics approaches, upregulation of ApoJ was found in high-fat medium-fed hepatocytes and livers of patients with NAFLD. Hepatic ApoJ level associated with the levels of mTOR and protein markers of autophagy and correlated positively with lipid contents in the liver of mice. Functionally, nonsecreted intracellular ApoJ bound to mTOR kinase domain and prevented mTOR ubiquitination by interfering FBW7 ubiquitin ligase interaction through its R324 residue. In vitro and in vivo gain-of-function or loss-of-function analysis further demonstrated that targeting ApoJ promotes proteasomal degradation of mTOR, restores lipophagy and lysosomal activity, thus prevents hepatic lipid deposition. Moreover, an antagonist peptide with a dissociation constant (Kd) of 2.54 µM interacted with stress-induced ApoJ and improved hepatic pathology, serum lipid and glucose homeostasis, and insulin sensitivity in mice with NAFLD or type II diabetes mellitus. CONCLUSIONS: ApoJ antagonist peptide might be a potential therapeutic against lipid-associated metabolic disorders through restoring mTOR and FBW7 interaction and facilitating ubiquitin-proteasomal degradation of mTOR.

Trench-assisted 12-core 5-LP mode fiber with a low refractive index circle and a high refractive index ring.

We propose a homogeneous five-mode twelve-core fiber with a trench-assisted structure, combining a low refractive index circle and a high refractive index ring (LCHR). The 12-core fiber utilizes the triangular lattice arrangement. The properties of the proposed fiber are simulated by the finite element method. The numerical result shows that the worst inter-core crosstalk (ICXT) can achieve at -40.14 dB/100 km, which is lower than the target value (-30 dB/100 km). Since adding the LCHR structure, the effective refractive index difference between LP21 and LP02 mode is 2.8 × 10-3, which illustrates that the LP21 and LP02 modes can be separated. In contrast to without the LCHR, the dispersion of LP01 mode has an apparent dropping, which is 0.16 ps/(nm·km) at 1550 nm. Moreover, the relative core multiplicity factor can reach 62.17, which indicates a large core density. The proposed fiber can be applied to the space division multiplexing system to enhance the fiber transmission channels and capacity.

Cation-π Interaction Trigger Supramolecular Hydrogelation of Peptide Amphiphiles.

As an important noncovalent interaction, cation-π interaction plays an essential role in a broad area of biology and chemistry. Despite extensive studies in protein stability and molecular recognition, the utilization of cation-π interaction as a major driving force to construct supramolecular hydrogel remains uncharted. Here, a series of peptide amphiphiles are designed with cation-π interaction pairs that can self-assemble into supramolecular hydrogel under physiological condition. The influence of cation-π interaction is thoroughly investigated on peptide folding propensity, morphology, and rigidity of the resultant hydrogel. Computational and experimental results confirm that cation-π interaction could serve as a major driving force to trigger peptide folding, resultant ß-hairpin peptide self-assembled into fibril-rich hydrogel. Furthermore, the designed peptides exhibit high efficacy on cytosolic protein delivery. As the first case of using cation-π interactions to trigger peptide self-assembly and hydrogelation, this work provides a novel strategy to generate supramolecular biomaterials.

Preparation and transmission characteristics of seven-core few-mode fiber with low loss and low inter-core crosstalk.

Seven-core five-mode fiber and single-core five-mode fiber with the same core structure by high and low refractive index double rings are prepared based on plasma chemical vapor deposition. The transmission characteristics of the single-core few-mode fiber and the seven-core few-mode fiber are measured and characterized by building an experimental platform. The prepared single-core few-mode fiber can stably transmit five LP modes at 1550 nm, which not only has low loss characteristics, but also has excellent bending resistance. Furthermore, the transmission loss of the prepared seven-core fiber is lower than 0.4 dB/km, and the inter-core crosstalk is lower than -50 dB/km, which realizes the high-density and low-crosstalk transmission of the multi-core fiber. The prepared seven-core few-mode fiber can solve the capacity limitation of single-mode fiber, which will contribute the development of future communication systems.

CT Characteristics of Acute Pancreatitis with Preexisting Fatty Liver and Its Impact on Pancreatitis Severity and Persistent Systemic Inflammatory Response Syndrome.

Purpose: To study the CT characteristics of acute pancreatitis (AP) associated with preexisting fatty liver (FL) and the impact of preexisting FL on the severity of AP and persistent systemic inflammatory response syndrome (SIRS). Patients and Methods: A total of 189 patients with AP were divided into AP with and without preexisting FL. The CT features, clinical characteristics, severity of AP, and presence of persistent SIRS between the two groups were compared. Univariate and multivariate analyses were performed to determine the risk factors for predicting SIRS. The diagnostic performances of the risk factors were evaluated by receiver operating characteristic (ROC) curve analysis. Results: Among the 189 patients, 49.7% (94/189) had preexisting FL. On CT, AP patients with preexisting FL were more likely to develop necrosis (23.4% vs 10.5%, p=0.021), local complications (45.7% vs 29.5%, p=0.025) and persistent SIRS (59.6% vs 27.4%, p<0.001). Multivariate analysis showed that preexisting FL (OR=2.863, 95% CI: 1.264-6.486, p=0.012), APACHE II≥6 (OR=1.334, 95% CI: 1.117-1.594, p=0.002), and MCTSI ≥4 (OR=1.489, 95% CI: 1.046-2.119, p=0.027) could be independent risk factors for persistent SIRS. The areas under the ROC curve of preexisting FL, APACHE II, and MCISI in diagnosing AP patients with persistent SIRS were 0.664, 0.703, and 0.783, respectively. Conclusion: Patients with preexisting FL were more likely to develop necrosis and local complications on CT and present more severe AP and persistent SIRS. Preexisting FL can be an independent risk factor in predicting the presence of persistent SIRS in patients with AP.

A nexus of social capital-based financing and farmers' scale operation, and its environmental impact.

The study constructs a theoretical model of social capital, farm household financing, and scale operation and their environmental effects, and conducts an empirical test based on data from China Family Panel Studies (CFPS) which is conducted in 2018 using causal mediation analysis. The results showed that farmers who spent more on human interaction have a higher probability of choosing scale operation by renting land, the mechanism of which is that the social capital accumulated by farmers based on human interaction facilitates their access to formal and informal financing, which in turn alleviates the financing constraint of scale operation. In addition, we found that the farmers with low education were more dependent on social capital to obtain informal financing to achieve scale operation. The environmental effects of scale operation found that the farmers significantly reduced the proportion of fertilizer and pesticide use, which could effectively mitigate possible pollution problems caused by excessive fertilizer and pesticide use. These findings confirm that social capital can alleviate the financing constraints of farmers to expand their operation scale through formal and informal financing, which in turn has a positive environmental effect.

Development of biomaterials based on plasticized polylactic acid and tea polyphenols for active-packaging application.

Bioactive-packaging films based on polylactic acid (PLA), acetyl tributyl citrate (ATBC), and tea polyphenol (TP) were prepared by melt blending. Results of mechanical-property test revealed that adding ATBC and TP can significantly improve mechanical properties of PLA. The shift of CO to lower wavelengths in FTIR and the morphology of the films in SEM indicated physical or chemical interactions in the PLA/ATBC/TP films. The antioxidant, and antibacterial activities of the PLA/ATBC films increased dramatically (P<0.05) with increased TP amount. The antioxidant activity of the films with 1 % TP was equivalent to that of 300 mg/L l-ascorbic acid, whereas PLA/ATBC/TP films with 0.5 % and 1 % TP concentration were effective in inhibiting Staphylococcus aureus and Escherichia coli within almost 5 h (P<0.05). The PLA films changed from transparent to opaque and from yellow to red after combining with ATBC or TP, respectively. The overall migration of the films in 3 % acetic acid and 10 % ethanol did not exceed the overall migration limit. All these findings indicated potential of the PLA/ATBC/TP films in active-packaging application.

Adiponectin, May Be a Potential Protective Factor for Obesity-Related Osteoarthritis.

Osteoarthritis (OA) is the most common joint disease in elderly individuals and seriously affects quality of life. OA has often been thought to be caused by body weight load, but studies have increasingly shown that OA is an inflammation-mediated metabolic disease. The current existing evidence suggests that OA is associated with obesity-related chronic inflammation as well as abnormal lipid metabolism in obesity, such as fatty acids (FA) and triglycerides. Adiponectin, a cytokine secreted by adipose tissue, can affect the progression of OA by regulating obesity-related inflammatory factors. However, the specific molecular mechanism has not been fully elucidated. According to previous research, adiponectin can promote the metabolism of FA and triglycerides, which indicates that it is a potential protective factor for OA through many mechanisms. This article aims to review the mechanisms of chronic inflammation, FA and triglycerides in OA, as well as the potential mechanisms of adiponectin in regulating chronic inflammation and promoting FA and triglyceride metabolism. Therefore, adiponectin may have a protective effect on obesity-related OA, which could provide new insight into adiponectin and the related mechanisms in OA.

The Complement and Coagulation Cascades Pathway is Associated with Acute Necrotizing Pancreatitis by Genomics and Proteomics Analysis.

Purpose: Acute pancreatitis can be classified histologically as interstitial edema pancreatitis (IEP) or as acute necrotizing pancreatitis (ANP). ANP has a higher mortality and long-term or short-term sequelae than IEP. Therefore, this work aims to explore the differences in pathogenesis between ANP and IEP and it has great clinical importance for the treatment and prevention of ANP. Methods: In this work, whole blood samples from IEP and ANP patients were analyzed by whole gene sequencing (WGS). Serum samples from IEP and ANP patients were evaluated via enzyme-linked immunosorbent assay (ELISA). Meanwhile, pancreatic tissues of IEP and ANP rat models were subjected to data independent acquisition (DIA) proteomics assays. Then, the WGS analysis and DIA proteomics assay data were analyzed comprehensively. Results: Six pathways were found to be significantly different in the ANP/IEP groups through WGS analysis. DIA proteomics found eleven different pathways. In both assays, the complement and coagulation cascades pathway was the most significantly different (p < 0.01) pathway between the two groups. WGS analysis showed base mutations in ten genes in the complement and coagulation cascades pathway. These results were consistent with the ten proteins detected by DIA proteomics analysis, which were significantly upregulated in the ANP/IEP groups. In addition, five of these proteins, complement C3, complement Factor I, alpha-2-macroglobulin, complement C9, and serpin family C member 1, were successfully verified by parallel reaction monitoring analysis and ELISA. Conclusion: C3, CFI, A2m, C9, and Serpinc1, which belong to complement and coagulation cascades pathway, may promote pancreatic necrosis and aggravate the severity of ANP.