[Advances in using artificial intelligence for predicting protein-ligand binding affinity].

The binding of proteins and ligands is a crucial aspect of life processes. The calculation of the protein-ligand binding affinity (PLBA) offers valuable insights into protein function, drug screening targets protein receptors, and enzyme modifications. In recent years, artificial intelligence (AI) has experienced rapid advancements, becoming widely used in PLBA prediction. This is attributed to its robust feature extraction ability, superior algorithm accuracy, and speedy calculations. Our paper aims to provide a comprehensive overview of AI predication process, associated resources, application scenarios, challenges, and potential solutions, serving as a valuable reference for the relevant research endeavors.

[Advances in mechanisms of biofilm formation and drug resistance of Staphylococcus aureus].

Staphylococcus aureus is a common pathogenic bacterium. However, due to the abuse of antibiotics, multiple drug-resistant S. aureus (DR S. aureus) has emerged in a large number, which seriously threatens human health. DR S. aureus usually forms biofilms by attaching on contact surfaces and secreting macromolecules including polysaccharides, proteins, and lipids, thus encasing themselves in a self-generated polymeric matrix. A biofilm provides an efficacious barrier that protects bacteria from detrimental environmental factors. Simultaneously, it protects DR S. aureus from the host immune system and attenuates the penetration and killing effects of drugs, serving as a key structure for the development of drug resistance. Therefore, gaining an in-depth understanding of the DR S. aureus biofilm is crucial for treating related infectious diseases. In this paper, we summarize recent research progress in the biofilm formation mechanism, drug resistance mechanism, and measures for inhibition and clearance of DR S. aureus and provide an outlook on the future research directions.

Metal-free, photoredox-catalyzed aromatization-driven deconstructive functionalization of spiro-dihydroquinazolinones with α-CF3 alkenes.

Metal-free, photoredox-catalyzed aromatization-driven deconstructive functionalization of spiro-dihydroquinazolinones with α-CF3 alkenes is presented. The readily available spiro-dihydroquinazolinones reacted efficiently with α-CF3 alkenes during photocatalysis to give the gem-difluoroallylated and the CF3-containing quinazolin-4(3H)-ones in good yields with excellent chemoselectivity. The selectivity depends on the electron effect of substituents in α-CF3 alkenes. A wide range of four-, five-, six-, seven-, eight- and twelve-membered spiro-dihydroquinazolinones were compatible with this transformation. The protocol is also characterized by the mild and redox-neutral reaction conditions, good functional group compatibility and excellent atom economy. Mechanistic studies revealed that the reaction proceeds via a radical pathway.

The interplay of psychological resilience and adolescent mobile phone addiction in Henan province, China: insights from latent class analysis.

Background: The aim of this study was to classify distinct subgroups of adolescents based on the severity levels of their mobile phone addiction and to investigate how these groups differed in terms of their psychosocial characteristics. We surveyed a total of 2,230 adolescents using three different questionnaires to assess the severity of their mobile phone addiction, stress, anxiety, depression, psychological resilience, and personality. Latent class analysis was employed to identify the subgroups, and we utilized Receiver Operating Characteristic (ROC) curves and multinomial logistic regression for statistical analysis. All data analyses were conducted using SPSS 26.0 and Mplus 8.5. Methods: We classified the subjects into subgroups based on their mobile phone addiction severity, and the results revealed a clear pattern with a three-class model based on the likelihood level of mobile phone addiction (p < 0.05). We examined common trends in psychosocial traits such as age, grade at school, parental education level, anxiety levels, and resilience. ROC analysis of sensitivity versus 1-specificity for various mobile phone addiction index (MPAI) scores yielded an area under the curve (AUC) of 0.893 (95% CI, 0.879 to 0.905, p < 0.001). We also determined diagnostic value indices for potential cutoff points ranging from 8 to 40. The optimal cutoff value for MPAI was found to be >14, which corresponded to the maximum Youden index (Youden index = 0.751). Results: The latent classification process in this research confirmed the existence of three distinct mobile phone user groups. We also examined the psychosocial characteristics that varied in relation to the severity levels of addiction. Conclusion: This study provides valuable insights into the categorization of adolescents based on the severity of mobile phone addiction and sheds light on the psychosocial characteristics associated with different addiction levels. These findings are expected to enhance our understanding of mobile phone addiction traits and stimulate further research in this area.

New Cytotoxic γ-Lactam Alkaloids from the Mangrove-Derived Fungus Talaromyces hainanensis sp. nov. Guided by Molecular Networking Strategy.

The fungus Talaromyces hainanensis, isolated from the mangrove soil, was characterized as a novel species by morphology observation and phylogenetic analyses. Four new γ-lactam alkaloids talaroilactams A-D (1-4) and two reported compounds harzianic acid (5) and isoharzianic acid (6) were identified from the fungus T. hainanensis WHUF0341, assisted by OSMAC along with molecular networking approaches. Their structures were determined through ECD calculations and spectroscopic analyses. Moreover, the biosynthetic route of 1-4 was also proposed. Compound 1 displayed potent cytotoxicity against HepG2 cell lines, with an IC50 value of 10.75 ± 1.11 µM. In addition, network pharmacology was employed to dissect the probable mechanisms contributing to the antihepatocellular carcinoma effects of compound 1, revealing that cytotoxicity was mainly associated with proteolysis, negative regulation of autophagy, inflammatory response, and the renin-angiotensin system. These results not only expanded the chemical space of natural products from the mangrove associated fungi but also afforded promising lead compounds for developing the antihepatocellular carcinoma agents.

Helicobacter pylori-Induced Angiopoietin-Like 4 Promotes Gastric Bacterial Colonization and Gastritis.

Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori-associated pathology are unknown. Here, we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA-dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a -/-, Angptl4 -/-, and Il17a -/- Angptl4 -/- mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K-AKT-NF-κB, resulting in increased gastric influx of regulatory CD4+ T cells (Tregs) via CCL5-CCR4-dependent migration. In turn, ANGPTL4 induced Treg proliferation by binding to ITGAV to activate PI3K-AKT-NF-κB, promoting H. pylori-associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection.

Prognostic value of mild asymptomatic intracranial atherosclerosis stenosis in patients with hypertension.

BACKGROUND AND AIMS: Mild asymptomatic intracranial atherosclerotic stenosis (aICAS) is common in Chinese patients with hypertension. However, there are no data on its prognostic value in this population. The aim of the present study was to clarify the prevalence and associated cardiovascular risk factors of mild aICAS and determine its prognostic value for overall and cardiovascular mortality in patients with hypertension. METHODS: In total, 1813 participants were evaluated for aICAS using computed tomographic angiography. The predictive effect of mild to severe aICAS on all-cause and cardiovascular mortality was evaluated using Kaplan-Meier survival curves and Cox regression analyses. RESULTS: The prevalence rate of mild aICAS was 35.7%. Poorly controlled hypertension, in combination with diabetes and dyslipidemia, was associated with aICAS. Patients with aICAS had an independently significant increase in the risk of all-cause and cardiovascular death, with adjusted hazard ratios (HRs) for mild to severe stenosis ranging from 1.52 to 3.03 for all-cause death and from 2.48 to 6.38 for cardiovascular death. Among the patients with mild aICAS, only those with more than two stenoses had increased mortality after adjustment, with an HR of 2.35 (95% CI: 1.36-4.04) for total death and 4.41 (95% CI: 1.78-10.93) for cardiovascular death. CONCLUSIONS: A significant association between mild aICAS and mortality in stroke-free patients with hypertension was revealed. The results indicate that mild aICAS might be an imaging marker for cerebrovascular lesions in patients with hypertension and poor control of blood pressure and lipids in this population requires further research.

Myeloid-derived suppressor cells-induced exhaustion of CD8 + T-cell participates in rejection after liver transplantation.

Liver transplantation (LT) rejection remains the most pervasive problem associated with this procedure, while the mechanism involved is still complicated and undefined. One promising solution may involve the use of myeloid-derived suppressor cells (MDSC). However, the immunological mechanisms underlying the effects of MDSC after LT remain unclear. This study is meant to clarify the role MDSCs play after liver transplantation. In this study, we collected liver tissue and peripheral blood mononuclear cells (PBMC) from LT patients showing varying degrees of rejection, as well as liver and spleen tissue samples from mice LT models. These samples were then analyzed using flow cytometry, immunohistochemistry and multiple immunofluorescence. M-MDSCs and CD8 + T-cells extracted from C57/BL6 mice were enriched and cocultured for in vitro experiments. Results, as obtained in both LT patients and LT mice model, revealed that the proportion and frequency of M-MDSC and PD-1 + T-cells increased significantly under conditions associated with a high degree of LT rejection. Within the LT rejection group, our immunofluorescence results showed that a close spatial contiguity was present between PD-1 + T-cells and M-MDSCs in these liver tissue samples and the proportion of CD84/PD-L1 double-positive M-MDSC was greater than that of G-MDSC. There was a positive correlation between the activity of CD84 and immunosuppressive function of M-MDSCs including PD-L1 expression and reactive oxygen species (ROS) production, as demonstrated in our in vitro model. M-MDSCs treated with CD84 protein were able to induce co-cultured CD8 + T-cells to express high levels of exhaustion markers. We found that CD84 regulated M-MDSC function via expression of PD-L1 through activation of the Akt/Stat3 pathway. These results suggest that the capacity for CD84 to regulate M-MDSC induction of CD8 + T-cell exhaustion may play a key role in LT rejection. Such findings provide important, new insights into the mechanisms of tolerance induction in LT.

Membrane protein MHZ3 regulates the on-off switch of ethylene signaling in rice.

Ethylene regulates plant growth, development, and stress adaptation. However, the early signaling events following ethylene perception, particularly in the regulation of ethylene receptor/CTRs (CONSTITUTIVE TRIPLE RESPONSE) complex, remains less understood. Here, utilizing the rapid phospho-shift of rice OsCTR2 in response to ethylene as a sensitive readout for signal activation, we revealed that MHZ3, previously identified as a stabilizer of ETHYLENE INSENSITIVE 2 (OsEIN2), is crucial for maintaining OsCTR2 phosphorylation. Genetically, both functional MHZ3 and ethylene receptors prove essential for OsCTR2 phosphorylation. MHZ3 physically interacts with both subfamily I and II ethylene receptors, e.g., OsERS2 and OsETR2 respectively, stabilizing their association with OsCTR2 and thereby maintaining OsCTR2 activity. Ethylene treatment disrupts the interactions within the protein complex MHZ3/receptors/OsCTR2, reducing OsCTR2 phosphorylation and initiating downstream signaling. Our study unveils the dual role of MHZ3 in fine-tuning ethylene signaling activation, providing insights into the initial stages of the ethylene signaling cascade.

Construction of Zn-Cu bimetallic metal-organic frameworks for carbon dioxide capture.

Bimetallic metal-organic frameworks (MOFs) have shown more impressive performance in gas adsorption compared with monometallic MOFs. Herein, a Cu-Zn bimetallic metal-organic framework (Zn/Cu-BTC) was synthesized via a one-pot method, and its structure, thermal stability and CO2 adsorption property were investigated and compared with those of corresponding monometallic Cu-BTC and Zn-BTC. The results showed that Zn/Cu-BTC has a specific ortho-octahedral crystal morphology with a unique X-ray diffraction peak, the atomic ratio of Zn to Cu is about 1 : 5, and it remained stable at a temperature up to 490 K. In Zn/Cu-BTC, Cu2+ played a role in increasing the specific surface area and porosity of the MOF and improving the gas adsorption performance. The CO2 adsorption of Zn/Cu-BTC is lower than that of Cu-BTC but much higher than that of Zn-BTC, and CO2 adsorption heat was 30.52 kJ mol-1, which indicated physical adsorption. In addition, Zn/Cu-BTC had higher CO2/N2 adsorption selectivity compared with Zn-BTC and Cu-BTC, with a maximum value of 17. This study can be a reference for the research on improving the adsorption selectivity of gases by constructing bimetallic MOFs.

Wafer-Scale Fabrication of Wearable All-Carbon Nanotube Photodetector Arrays.

With electronic devices evolving toward portable and high-performance wearables, the constraints of complex and wet processing technologies become apparent. This study presents a scalable photolithography/chemical-free method for crafting wearable all-carbon nanotube (CNT) photodetector device arrays. Laser-assisted patterning and dry deposition techniques directly assemble gas-phase CNTs into flexible devices without any lithography or lift-off processes. The resulting wafer-scale all-CNT photodetector arrays showcase excellent uniformity, wearability, environmental stability, and notable broadband photoresponse, boasting a high responsivity of 44 AW-1 and a simultaneous detectivity of 1.9 × 109 Jones. This research provides an efficient, versatile, and scalable strategy for manufacturing wearable all-CNT device arrays, allowing widespread adoption in wearable optoelectronics and multifunctional sensors.

Fluoride-resistant Streptococcus mutans within cross-kingdom biofilms support Candida albicans growth under fluoride and attenuate the in vitro anti-caries effect of fluorine.

Fluoride-resistant Streptococcus mutans (S. mutans) might affect the ecological balance of biofilms in the presence of fluoride. We used a S. mutans and Candida albicans (C. albicans) cross-kingdom biofilm model to investigate whether fluoride-resistant S. mutans in biofilms would support C. albicans growth under fluoride stress and attenuate the in vitro anti-caries effect of fluorine. The impact of fluoride-resistant S. mutans on formation of cross-kingdom biofilms by S. mutans and C. albicans in the presence of fluoride was investigated in vitro using the crystal violet staining assay. Biofilm constitution was determined using colony-forming unit (CFU) counts and fluorescent in situ hybridization (FISH). Extracellular polysaccharide (EPS) generation in biofilms was determined by EPS/bacterial dying and water-insoluble polysaccharide detection. Acid production and demineralization were monitored using pH, lactic acid content, and transversal microradiography (TMR). The gene expression of microorganisms in the cross-kingdom biofilm was measured using qRT-PCR. Our results showed that both C. albicans and fluoride-resistant S. mutans grew vigorously, forming robust cross-kingdom biofilms, even in the presence of sodium fluoride (NaF). Moreover, fluoride-resistant S. mutans-containing cross-kingdom biofilms had considerable cariogenic potential for EPS synthesis, acid production, and demineralization ability in the presence of NaF than fluoride-sensitive S. mutans-containing biofilms. Furthermore, the gene expression of microorganisms in the two cross-kingdom biofilms changed dissimilarly in the presence of NaF. In summary, fluoride-resistant S. mutans in cross-kingdom biofilms supported C. albicans growth under fluoride and might attenuate the anti-caries potential of fluorine by maintaining robust cross-kingdom biofilm formation and cariogenic virulence expression in vitro in the presence of NaF.

Predictors of early colorectal cancer metastasis to lymph nodes: providing rationale for therapy decisions.

With the improvement of national health awareness and the popularization of a series of screening methods, the number of patients with early colorectal cancer is gradually increasing, and accurate prediction of lymph node metastasis of T1 colorectal cancer is the key to determining the optimal therapeutic solutions. Whether patients with T1 colorectal cancer undergoing endoscopic resection require additional surgery and regional lymph node dissection is inconclusive in current guidelines. However, we can be sure that in early colorectal cancer without lymph node metastasis, endoscopic resection alone does not affect the prognosis, and it greatly improves the quality of life and reduces the incidence of surgical complications while preserving organ integrity. Therefore, it is vital to discriminate patients without lymph node metastasis in T1 colorectal cancer, and this requires accurate predictors. This paper briefly explains the significance and shortcomings of traditional pathological factors, then extends and states the new pathological factors, clinical test factors, molecular biomarkers, and the risk assessment models of lymph node metastasis based on artificial intelligence.

The High Resistance Loop (H-Loop) Technique for Arthroscopic Repair of Subscapularis.

The subscapularis tendon is more challenging and riskier to repair than the posterior upper rotator cuff. The knotless anchor suture in subscapularis repair simplified the repair process and had an excellent postoperative effect. We describe a new knotless anchor stitching method, the H-Loop technique. The simplicity and efficiency of the technique make it particularly suitable for small subscapular tendon tears.

Cryo-EM Structure and Biochemical Analysis of the Human Chemokine Receptor CCR8.

The C-C motif chemokine receptor 8 (CCR8) is a class A G-protein-coupled receptor that has emerged as a promising therapeutic target in cancer and autoimmune diseases. In the present study, we solved the cryo-electron microscopy (cryo-EM) structure of the human CCR8-Gi complex in the absence of a ligand at 2.58 Å. Structural analysis and comparison revealed that our apo CCR8 structure undergoes some conformational changes and is similar to that in the CCL1-CCR8 complex structure, indicating an active state. In addition, the key residues of CCR8 involved in the recognition of LMD-009, a potent nonpeptide agonist, were investigated by mutating CCR8 and testing the calcium flux induced by LMD-009-CCR8 interaction. Three mutants of CCR8, Y1133.32A, Y1724.64A, and E2867.39A, showed a dramatically decreased ability in mediating calcium mobilization, indicating their key interaction with LMD-009 and key roles in activation. These structural and biochemical analyses enrich molecular insights into the agonism and activation of CCR8 and will facilitate CCR8-targeted therapy.

Functional partitioning synergistically enhances multi-scenario nitrate reduction.

The promising electrocatalytic nitrate reduction reaction (eNitRR) for distributed ammonia synthesis requires the fine design of functionally compartmentalised and synergistically complementary integrated catalysts to meet the needs of low-cost and efficient ammonia synthesis. Herein, the partitionable CoP3 and Cu3P modules were built on the copper foam substrate, and the functional differentiation promoted the catalytic performance of the surface accordion-like CoP3/Cu3P@CF for eNitRR in complex water environment. Where the ammonia yield rate is as high as 23988.2 µg h-1 cm-2, and the Faradaic efficiency is close to 100 %. With CoP3/Cu3P@CF as the core, the assembled high-performance Zn-nitrate flow battery can realize the dual function of ammonia production and power supply, and can also realize the continuous production of ammonia with high selectivity driven by solar energy. The ammonia recovery reaches 753.9 mg L-1, which shows the superiority of CoP3/Cu3P@CF in multiple application scenarios and provides important experience for the vigorous development of eNitRR. Density functional theory calculation reveal that CoP3 and Cu3P sites play a relay synergistic role in eNitRR catalyzed by CoP3/Cu3P@CF. CoP3 first promotes the activation of NO3- to *NO3H, and then continuously provides proton hydrogen for the eNitRR on the surface of Cu3P, which relays the synergistic catalytic effect to promote the efficient conversion of NO3- to NH3. This study not only develops a catalyst that can promote the efficient reduction of NO3- to ammonia through an easy-to-obtain innovative strategy, but also provides an alternative strategy for the development of eNitRR that is suitable for multiple scenarios and meets the production conditions.

Serum and Urine Metabolic Fingerprints Characterize Renal Cell Carcinoma for Classification, Early Diagnosis, and Prognosis.

Renal cell carcinoma (RCC) is a substantial pathology of the urinary system with a growing prevalence rate. However, current clinical methods have limitations for managing RCC due to the heterogeneity manifestations of the disease. Metabolic analyses are regarded as a preferred noninvasive approach in clinics, which can substantially benefit the characterization of RCC. This study constructs a nanoparticle-enhanced laser desorption ionization mass spectrometry (NELDI MS) to analyze metabolic fingerprints of renal tumors (n = 456) and healthy controls (n = 200). The classification models yielded the areas under curves (AUC) of 0.938 (95% confidence interval (CI), 0.884-0.967) for distinguishing renal tumors from healthy controls, 0.850 for differentiating malignant from benign tumors (95% CI, 0.821-0.915), and 0.925-0.932 for classifying subtypes of RCC (95% CI, 0.821-0.915). For the early stage of RCC subtypes, the averaged diagnostic sensitivity of 90.5% and specificity of 91.3% in the test set is achieved. Metabolic biomarkers are identified as the potential indicator for subtype diagnosis (p < 0.05). To validate the prognostic performance, a predictive model for RCC participants and achieve the prediction of disease (p = 0.003) is constructed. The study provides a promising prospect for applying metabolic analytical tools for RCC characterization.

Prevalence of subthreshold depression and its related factors in Chinese college students: A cross-sectional study.

Objective: To investigate the prevalence of subthreshold depression among Chinese college students and to explore the related factors. Methods: The research subjects were Chinese college students participating in the "2022 Psychology and Behavior Investigation of Chinese Residents (PBICR-2022)". Data on respondents' general characteristics, quality of life, perceived pressure, family communication, perceived social support, self-efficacy, and depression status were gathered. To investigate the association between each variable and the risk of subthreshold depression, statistical analyses, including chi-square tests and rank sum tests were conducted. Furthermore, a binary stepwise logistic regression was employed to establish the regression model of the factors related to subthreshold depression among Chinese college students. Results: A prevalence of subthreshold depression of about 39.7 % was found among the 8934 respondents. Logistic regression analysis revealed that respondents who are female, have chronic diseases, are in debt, experience significant impacts from epidemic control policies, have lower self-assessed quality of life, experience challenges in family communication, perceive lower social support, have lower self-efficacy, and feel higher perceived pressure are more likely to develop subthreshold depression compared to the control group. (P < 0.05). Conclusion: The prevalence rate of subthreshold depression among Chinese college students was found to be approximately 40 %. Female college students suffering from chronic diseases, with households in debt, greatly impacted by epidemic control policies, and experiencing high perceived stress, may be at risk for subthreshold depression among Chinese college students. On the other hand, strong family communication, perceived social support, and self-efficacy were identified as potential protective factors. In order to facilitate timely screening, diagnosis, and treatment of subthreshold depression in Chinese college students, it is crucial for the government, local communities, colleges, and families to prioritize the mental health of college students and implement targeted measures accordingly.

Network pharmacology analysis of the regulatory effects and mechanisms of ALAE on sow reproduction in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Reproductive ability of sows is a primary element influencing the development of pig farming. Herbal extracts of Angelica sinensis (Oliv.) Diels, Astragalus mongholicus Bunge, Eucommia ulmoides Oliv., and Polypodium glycyrrhiza D.C.Eaton showed effects on improvement of reproduction in sows. AIMS OF THE STUDY: To investigate the mechanism of the treatment effects by a compound of these four Chinese herbs in a 1:1:1:1 ratio (ALAE) on endometriosis, endometritis, uterine adhesion, intrauterine growth retardation, pre-eclampsia, and its enhancement of reproductive efficiency in sows. MATERIALS AND METHODS: Active components of ALAE were identified by using ultra-performance liquid chromatography-mass spectrometry analysis and network pharmacology. Then we used the results to construct a visualization network. Key targets and pathways of ALAE involved in sow reproduction improvement were validated in sow animals and porcine endometrial epithelial cells (PEECs). RESULTS: A total of 62 active compounds were found in ALAE (41 in Polypodium glycyrrhiza D.C.Eaton, 5 in Astragalus mongholicus Bunge, 11 in Eucommia ulmoides Oliv., 5 in Angelica sinensis (Oliv.) Diels) with 563 disease-related targets (e.g. caspase-3, EGFR, IL-6) involved in EGFR tyrosine kinase inhibitor resistance, PI3K-AKT, and other signaling pathways. Molecular docking results indicated GC41 (glabridin), GC18 (medicarpin), EGFR and CCND1 are possible key components and target proteins related to reproductive improvement in sows. In PEECs, EGFR expression decreased at the mRNA and protein levels by three doses (160, 320, and 640 µg/mL) of ALAE. The phosphorylation of downstream pathway PI3K-AKT1was enhanced. The expression of inflammatory factors (IL-6, IL-1ß), ESR1 and caspase-3 decreased through multiple pathways. Additionally, the expression levels of an anti-inflammatory factor (IL-10), angiogenesis-related factors (MMP9, PIGF, PPARγ, IgG), and placental junction-related factors (CTNNB1, occludin, and claudin1) increased. Furthermore, the total born number of piglets, the number of live and healthy litters were significantly increased. The number of stillbirths decreased by ALAE treatment in sow animals. CONCLUSIONS: Dministration of ALAE significantly increased the total number of piglets born, the numbers of live and healthy litters and decreased the number of stillbirths through improving placental structure, attenuating inflammatory response, modulating placental angiogenesis and growth factor receptors in sows. The improvement of reproductive ability may be related to activation of the EGFR-PI3K-AKT1 pathway in PEECs. Moreover, ALAE maybe involved in modulation of estrogen receptors, apoptotic factors, and cell cycle proteins.