Dissolved organic matter characteristics linked to bacterial community succession and nitrogen removal performance in woodchip bioreactors.

Woodchip bioreactors are an eco-friendly technology for removing nitrogen (N) pollution. However, there needs to be more clarity regarding the dissolved organic matter (DOM) characteristics and bacterial community succession mechanisms and their association with the N removal performance of bioreactors. The laboratory woodchip bioreactors were continuously operated for 360 days under three influent N level treatments, and the results showed that the average removal rate of TN was 45.80 g N/(m3·day) when the influent N level was 100 mg N/L, which was better than 10 mg N/L and 50 mg N/L. Dynamic succession of bacterial communities in response to influent N levels and DOM characteristics was an important driver of TN removal rates. Medium to high N levels enriched a copiotroph bacterial module (Module 1) detected by network analysis, including Phenylobacterium, Xanthobacteraceae, Burkholderiaceae, Pseudomonas, and Magnetospirillaceae, carrying N-cycle related genes for denitrification and ammonia assimilation by the rapid consumption of DOM. Such a process can increase carbon limitation to stimulate local organic carbon decomposition to enrich oligotrophs with fewer N-cycle potentials (Module 2). Together, this study reveals that the compositional change of DOM and bacterial community succession are closely related to N removal performance, providing an ecological basis for developing techniques for N-rich effluent treatment.

Mutual regulation of microglia and astrocytes after Gas6 inhibits spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202502000-00032/figure1/v/2024-05-28T214302Z/r/image-tiff Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury. Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction. However, the mechanisms involved remain unclear. In this study, we found that after spinal cord injury, resting microglia (M0) were polarized into pro-inflammatory phenotypes (MG1 and MG3), while resting astrocytes were polarized into reactive and scar-forming phenotypes. The expression of growth arrest-specific 6 (Gas6) and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury. In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia, and even inhibited the cross-regulation between them. We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway. This, in turn, inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways. In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord, thereby promoting tissue repair and motor function recovery. Overall, Gas6 may play a role in the treatment of spinal cord injury. It can inhibit the inflammatory pathway of microglia and polarization of astrocytes, attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment, and thereby alleviate local inflammation and reduce scar formation in the spinal cord.

Short-term choroidal changes as early indicators for future myopic shift in primary school children: results of a 2-year cohort study.

BACKGROUND: To assess predictive value of short-term choroidal changes for future myopic shift in children. METHODS: 577 eyes of 289 primary school children were prospectively followed for 2 years. Cycloplegic refractions at baseline, 1 year and 2 years, and choroidal measurements by optical coherence tomography at baseline and 3 months, were used for analyses. Myopic shift was defined as refraction change of at least -0.50 dioptre/year, at 2 years compared with baseline. RESULTS: 228 participants (455 eyes) completed 2-year follow-up. Approximately 37.6% of 311 initially non-myopic eyes and 73.6% of 144 initially myopic eyes developed a myopic shift. Notably, at 3 months greater reductions were found in initially myopic eyes with myopic shift, than in those without myopic shift-in choroidal thickness (ChT), luminal area (LA), stromal area (SA) and total choroidal area (TCA), but no significant differences in any choroidal parameters were observed between non-myopic eyes, with and without myopic shift. Multivariable analyses showed that in myopic eyes, each percentage increase in ChT, LA, SA and TCA was associated with reduced odds of myopic shift (all p<0.001). Similar associations were observed in non-myopic eyes, with smaller effects than in myopic eyes. Adding a 3-month percentage change of each choroidal parameter to a basic model including age, gender, parental myopia and baseline refraction significantly improved the predictive performance in myopic eyes (area under the receiver operating characteristic curves increasing from 0.650 to approximately 0.800, all p<0.05), but not in non-myopic eyes. CONCLUSION: Short-term choroidal changes could act as early indicators for future myopic shift in children.

Interpersonal interactions, sense of loneliness and perceived depressive emotions among older adults: A cultural-psychological perspective from heterogeneous roles of different relationships.

In the context of the "Chinese Differential Mode of Association" in traditional Chinese culture, this paper examines the heterogeneous effects of interpersonal interactions in different relationships on older adults' depressive emotions from a cultural-psychological perspective. Results using data from Chinese General Social Survey demonstrate that: interactions with children are the most helpful in reducing perceived depression for the elderly, followed by communications with siblings and relatives. However, interactions with friends and other fellows do not significantly reduce older people's perceived depression. This reflects the "Chinese Differential Mode of Association" in interpersonal relationships. When using different perceived depression measures, and Double Debiased Machine Learning (DDML) approaches for robustness and endogeneity tests, above findings are very robust. The impact mechanism is that interactions with children and siblings reduce depressive emotions by decreasing older adults' sense of loneliness, while communications with others do not have such a significant effect. This paper further discusses the roles of different types of interactions with adult children. It is found that receiving and providing emotional support can prominently decrease depressive emotions for older people, whereas the effects of monetary support and non-material assistance are less pronounced. In addition, interpersonal interactions' impacts are more significant for those who are female, older than 75 and with poorer health, as well as older people who exercise less frequently, have higher social status, and hold more traditional beliefs. In the current context of active promotion of healthy aging, findings of this paper have important implications for a deeper understanding and scientific management of depressive emotions among the elderly.

Semi-synthetic chondroitin sulfate CS-semi5 upregulates miR-122-5p, conferring a therapeutic effect on osteoarthritis via the p38/MMP13 pathway.

Osteoarthritis (OA) is an aging-associated disease characterized by joint stiffness pain and destroyed articular cartilage. Traditional treatments for OA are limited to alleviating various OA symptoms. There is a lack of drugs available in clinical practice that can truly repair cartilage damage. Here, we developed the chondroitin sulfate analog CS-semi5, semi-synthesized from chondroitin sulfate A. In vivo, CS-semi5 alleviated inflammation, provided analgesic effects, and protected cartilage in the modified Hulth OA rat model and papain-induced OA rat model. A bioinformatics analysis was performed on samples from OA patients and an exosome analysis on papain-induced OA rats, revealing miR-122-5p as the key regulator associated with CS-semi5 in OA treatment. Binding prediction revealed that miR-122-5p acted on the 3'-untranslated region of p38 mitogen-activated protein kinase, which was related to MMP13 regulation. Subsequent in vitro experiments revealed that CS-semi5 effectively reduced cartilage degeneration and maintained matrix homeostasis by inhibiting matrix breakdown through the miR-122-5p/p38/MMP13 axis, which was further validated in the articular cartilage of OA rats. This is the first study to investigate the semi-synthesized chondroitin sulfate CS-semi5, revealing its cartilage-protecting, anti-inflammatory, and analgesic properties that show promising therapeutic effects in OA via the miR-122-5p/p38/MMP13 pathway.

Integrating network analysis and experimental validation to reveal the mechanism of si-jun-zi decoction in the treatment of renal fibrosis.

Treating kidney diseases from the perspective of spleen is an important clinical method in traditional Chinese medicine (TCM) for anti-renal fibrosis (RF). Si-jun-zi decoction (SJZD), a classic formula for qi-invigorating and spleen-invigorating, has been reported to alleviate RF. This study aims to investigate the potential mechanism by which SJZD attenuates RF. The results demonstrated notable improvements in renal function levels, inflammation and fibrosis indices in UUO-mice following SJZD intervention. The main active ingredients identified were Quercetin, Kaempferol, Naringenin and 7-Methoxy-2-methyl isoflavone. Furthermore, STAT3, MAPK3, MYC were confirmed as key targets. Additionally, GO enrichment analysis demonstrated that SJZD delayed RF primarily by regulating oxidative stress and other biological mechanisms. KEGG enrichment analysis revealed the involvement of pathways such as Lipid and atherosclerosis signaling pathway, MAPK signaling pathway and other pathways in the reno-protective effects of SJZD. The molecular docking results revealed that the active ingredients of SJZD were well-bound and stable to the core targets. The experiments results revealed that Quercetin, Kaempferol, and Naringenin not only improved the morphology of TGF-ß-induced HK-2 cells but also reversed the expression of α-SMA, COL1A1 and MAPK, thereby delaying the progression of RF. The anti-RF effects of SJZD were exerted through multi-components, multi-targets and multi-pathways.

Sialyl Lewis X decorated integrin α3 on small extracellular vesicles promotes metastasis of bladder cancer via enhancing vascular permeability.

The permeability of blood vessels plays a crucial role in the spread of cancer cells, facilitating their metastasis at distant sites. Small extracellular vesicles (sEVs) are known to contribute to the metastasis of various cancers by crossing the blood vessel wall. However, the role of abnormal glycoconjugates on sEVs in tumor blood vessels remains unclear. Our study found elevated levels of fucosyltransferase VII (FUT7) and its product sialyl Lewis X (sLeX) in muscle-invasive bladder cancer (BLCA), with high levels of sLeX promoting the growth and invasion of BLCA cells. Further investigation revealed that sLeX was enriched in sEVs derived from BLCA. sLeX-decorated sEVs increased blood vessel permeability by disrupting the tight junctions of human umbilical vein endothelial cells (HUVECs). Using the glycoproteomics approach, we identified integrin α3 (ITGA3) as a sLeX-bearing glycoprotein in BLCA cells and their sEVs. Mechanically, sLeX modification stabilized ITGA3 by preventing its degradation in lysosomes. sEVs carrying sLeX-modified ITGA3 can be effectively internalized by HUVECs, leading to a decrease in the expression of tight junction protein. Conversely, silencing ITGA3 in sLeX-decorated sEVs restored tight junction proteins and reduced blood vessel permeability by inhibiting the MAPK pathway. Moreover, sLeX-modification of ITGA3 at Asn 265 in HUVECs promoted occludin dephosphorylation at Ser/Thr residues, followed by inducing its importin α1-mediated nuclear translocation, which resulted in the disruption of tight junctions. Our findings suggest a potential strategy for disrupting the formation of a metastatic microenvironment and preventing the spread of malignant bladder cancer.

Earthworms Enhance Crop Resistance to Insects Under Microplastic Stress by Mobilizing Physical and Chemical Defenses.

To assess the ecological risk of microplastics (MPs) in agricultural systems, it is critical to simultaneously focus on MP-mediated single-organism response and different trophic-level organism interaction. Herein, we placed earthworms in soils contaminated with different concentrations (0.02% and 0.2% w/w) of polyethylene (PE) and polypropylene (PP) MPs to investigate the effect of earthworms on tomato against Helicoverpa armigera (H. armigera) under MPs stress. We found that earthworms alleviated the inhibitory effects of MPs stress on tomato growth and disrupted H. armigera growth. Compared to individual MPs exposure, earthworm incorporation significantly increased the silicon and lignin content in herbivore-damaged tomato leaves by 19.1% and 57.6%, respectively. Metabolites involved in chemical defense (chlorogenic acid) and phytohormones (jasmonic acid) were also activated by earthworm incorporation. Furthermore, earthworms effectively reduced oxidative damage induced by H. armigera via promoting antioxidant metabolism. Overall, our results suggest that utilizing earthworms to regulate above- and below-ground interactions could be a promising strategy for promoting green agriculture.

Sludge-derived hydrochar modulates complete nonradical electron transfer in peroxydisulfate activation via pyrrolic-N and carbon defect: Implication for degrading electron-rich ionizable anilines compounds.

Nonradical electron transfer process (ETP) is a promising pathway for pollutant degradation in peroxydisulfate-based advanced oxidation processes (PDS-AOPs). However, there is a critical bottleneck to trigger ETP by sludge-derived hydrochar due to its negatively charged surface, inferior porosity and electrical conductivity. Herein, pyrrolic-N doped and carbon defected sludge-derived hydrochar (SDHC-N) was constructed for PDS activation to degrade anilines ionizable organic compounds (IOC) through complete nonradical ETP oxidation. Degradation of anilines IOC was not only affected by the electron-donating capacity but also proton concentration in solution because of the ionizable amino group (-NH2). Diverse effects including proton favor, insusceptible and inhibition were observed. Impressively, addition of HCO3 with strong proton binding capacity boosted aniline degradation nearly 10 times. Moreover, characterizations and theoretical calculations demonstrated that pyrrolic-N increased electron density and created positively charged surface, profoundly promoting generation of SDHC-N-S2O82-* complexes. More delocalized electrons around carbon defect could enhance electron mobility. This work guides a rational design of sludge-derived hydrochar to mediate nonradical ETP oxidation, and provides insights into the impacts of proton on anilines IOC degradation.

Nature of back slopping kombucha fermentation process: insights from the microbial succession, metabolites composition changes and their correlations.

Kombucha, a fermented tea prepared with a symbiotic culture of bacteria and yeast (SCOBY), offers a unique and unpredictable home-brewed fermentation process. Therefore, the need for a controlled kombucha fermentation process has become evident, which requiring a thorough understanding of the microbial composition and its relationship with the metabolites produced. In this study, we investigated the dynamics of microbial communities and metabolites over a 12-day fermentation period of a conventional kombucha-making process. Our findings revealed similarities between the microbial communities in the early (0-2 days) and late (10-12 days) fermentation periods, supporting the principle of back-slopping fermentation. Untargeted metabolite analysis unveiled the presence of harmful biogenic amines in the produced kombucha, with concentrations increasing progressively throughout fermentation, albeit showing relatively lower abundance on days 8 and 12. Additionally, a contrasting trend between ethanol and caffeine content was observed. Canonical correspondence analysis highlighted strong positive correlations between specific bacterial/yeast strains and identified metabolites. In conclusion, our study sheds light on the microbial and metabolite dynamics of kombucha fermentation, emphasizing the importance of microbial control and quality assurance measures in the production process.

Endoplasmic reticulum-targeted delivery of celastrol and PD-L1 siRNA for reinforcing immunogenic cell death and potentiating cancer immunotherapy.

The prospect of employing chemoimmunotherapy targeted towards the endoplasmic reticulum (ER) presents an opportunity to amplify the synergistic effects of chemotherapy and immunotherapy. In this study, we initially validated celastrol (CEL) as an inducer of immunogenic cell death (ICD) by promoting ER stress and autophagy in colorectal cancer (CRC) cells. Subsequently, an ER-targeted strategy was posited, involving the codelivery of CEL with PD-L1 small interfering RNAs (siRNA) using KDEL peptide-modified exosomes derived from milk (KME), to enhance chemoimmunotherapy outcomes. Our findings demonstrate the efficient transportation of KME to the ER via the Golgi-to-ER pathway. Compared to their non-targeting counterparts, KME exhibited a significant augmentation of the CEL-induced ICD effect. Additionally, it facilitated the release of danger signaling molecules (DAMPs), thereby stimulating the antigen-presenting function of dendritic cells and promoting the infiltration of T cells into the tumor. Concurrently, the ER-targeted delivery of PD-L1 siRNA resulted in the downregulation of both intracellular and membrane PD-L1 protein expression, consequently fostering the proliferation and activity of CD8+ T cells. Ultimately, the ER-targeted formulation exhibited enhanced anti-tumor efficacy and provoked anti-tumor immune responses against orthotopic colorectal tumors in vivo. Collectively, a robust ER-targeted delivery strategy provides an encouraging approach for achieving potent cancer chemoimmunotherapy.

Immunogenomic features of radiologically distinctive nodules in multiple primary lung cancer.

OBJECTIVES: To provide molecular and immunological attributes mechanistic insights for the management of radiologically distinctive multiple primary lung cancer (MPLC). METHODS: The Bulk RNA-seq data of MPLC were obtained from our center. The Bulk RNA-seq data and CT images of patients with single primary lung cancer (SPLC) were obtained from GSE103584. Immune infiltration algorithms were performed to investigate the disparities in the immunological microenvironment between the two groups. Single-cell gene analysis was used to explore immune cells composition and communication relationships between cells in MPLC. RESULTS: In MPLC, 11 pure ground-glass opacity nodules (pGGN) and 10 mixed GGN (mGGN) were identified, while in SPLC, the numbers were 18 pGGN and 22 mGGN, respectively. In MPLC, compared to pGGN, mGGN demonstrated a significantly elevated infiltration of CD8+ T cells. Single-cell gene analysis demonstrated that CD8+ T cells play a central role in the signaling among immune cells in MPLC. The transcription factors including MAFG, RUNX3, and TBX21 may play pivotal roles in regulation of CD8+ T cells. Notably, compared to SPLC nodules for both mGGN and pGGN, MPLC nodules demonstrated a significantly elevated degree of tumor-infiltrating immune cells, with this difference being particularly pronounced in mGGN. There was a positive correlation between the proportion of immune cells and consolidation/tumor ratio (CTR). CONCLUSIONS: Our findings provided a comprehensive description about the difference in the immune microenvironment between pGGN and mGGN in early-stage MPLC, as well as between MPLC and SPLC for both mGGN and pGGN. The findings may provide evidence for the design of immunotherapeutic strategies for MPLC.

Soil microbial community composition and nitrogen enrichment responses to the operation of electric power substation.

The surge in global energy demand mandates a significant expansion of electric power substations. Nevertheless, the ecological consequences of electric power substation operation, particularly concerning the electromagnetic field, on soil microbial communities and nitrogen enrichment remain unexplored. In this study, we collected soil samples from six distinct sites at varying distances from an electric power substation in Xintang village, southeastern China, and investigated the impacts of electromagnetic field on the microbial diversity and community structures employing metagenomic sequencing technique. Our results showed discernible dissimilarities in the fungal community across the six distinct sites, each characterized by unique magnetic and electric intensities, whereas comparable variations were not evident within bacterial communities. Correlation analysis revealed a diminished nitrogen fixation capacity at the site nearest to the substation, characterized by low moisture content, elevated pH, and robust magnetic induction intensity and electric field intensity. Conversely, heightened nitrification processes were observed at this location compared to others. These findings were substantiated by the relative abundance of key genes associated with ammonium nitrogen and nitrate nitrogen production. This study provides insights into the relationships between soil microbial communities and the enduring operation of electric power substations, thereby contributing fundamental information essential for the rigorous environmental impact assessments of these facilities.

Microfluidic-Assisted Pneumatic Droplet Generators Designed for Multiscenario Biomanufacturing with Favorable Biocompatibility and Extendibility.

Droplets, tiny liquid compartments, are increasingly emerging in the biomedical and biomanufacturing fields due to their unique properties to serve as templates or independent reaction units. Currently, the straightforward and efficient generation of various functional droplets in a biofriendly manner remains challenging. Herein, a novel microfluidic-assisted pneumatic strategy is described for the customizable and high-throughput production of monodispersed droplets, and the droplet size can be precisely controlled via a simplified gas pressure regulation module. In particular, numerous uniform alginate microcarriers can be rapidly fabricated in an all-aqueous manner, wherein the encapsulated islet or liver cells exhibit favorable viability and biological functions. Furthermore, by changing the microchannel configuration, several fluid manipulation functions developed by microfluidic technology, such as mixing and laminar flow, can be successfully incorporated into this platform. The droplet generators with scalable functionality are demonstrated in many biomanufacturing scenarios, including on-demand distribution of cell-mimetic particles, continuous synthesis of biomedical metal-organic framework (MOF), controllable preparation of compartmental microgel, etc. These may provide sustainable inspiration for developing droplet generators and their applications in tissue and organ engineering, biomaterials design, bioprinting nozzles, and other fields.

Highly sensitive SERS detection of melamine based on 3D Ag@porous silicon photonic crystal.

The stability, reproducibility and engineering of SERS substrate faces a great challenge in melamine SERS assay. In this work, a simple, highly sensitive, stable and cost-efficient SERS detection platform for melamine was established based on its Raman fingerprints spectrum. The Ag@ porous silicon photonic crystal (Ag@PPC) was prepared as the 3D SERS substrate by electrochemical etching and magnetron sputter technology. The main influence factors for the preparation of SERS substrate were investigated in detail. The analytical enhancement factor of the 3D SERS substrate can reach to 2.6 × 108. The 3D SERS detection platform showed a wide linear detection range of 10-4∼10 mg L-1 and a low limit of detection of 0.1 µg L-1 for melamine. Moreover, such detection platform showed good stability, high reproducibility and high recovery rates for melamine. The 3D Ag@PPC SERS substrate can be easily prepared and engineered, displaying a great potential application in food safety field.

An ultrasensitive and specific fluorescence split-aptasensor for VEGF165 detection based on nicking enzyme-assisted 3D DNA walker coupling with CRISPR-Cas12a.

The overexpression of vascular endothelial growth factor 165 (VEGF165) in cancer cells plays a pivotal role in promoting tumor metastasis by facilitating their excessively rapid proliferation and division. Hence, the development of analytical methods possessing high sensitivity and resistance to interference is imperative for the detection of VEGF165. Various types of aptasensors have been devised for VEGF165 detection; however, the performance of these biosensors can be influenced by non-target signals caused by conformational changes in unbound aptamers. The paper shows the creation of a precise and sensitive fluorescence biosensor designed to detect VEGF165 by using a VEGF165-specific split aptamer. Additionally, this biosensor employs nicking enzyme-assisted DNA walker coupling with CRISPR-Cas12a to achieve dual-signal amplification. The VEGF165 calibration curve shows a detection limit of 268 fM and has a broad linear range from 5 to 4000 nM. The fluorometric biosensor was utilized to detect VEGF165 in human serum and cellular homogenate samples, yielding good outcomes. The innovative design serves as proof of concept and demonstrates significant potential in detecting various targets.

Genome-wide identification and evolution of the SAP gene family in sunflower (Helianthus annuus L.) and expression analysis under salt and drought stress.

Stress-associated proteins (SAPs) are known to play an important role in plant responses to abiotic stresses. This study systematically identified members of the sunflower SAP gene family using sunflower genome data. The genes of the sunflower SAP gene family were analyzed using bioinformatic methods, and gene expression was assessed through fluorescence quantification (qRT-PCR) under salt and drought stress. A comprehensive analysis was also performed on the number, structure, collinearity, and phylogeny of seven Compositae species and eight other plant SAP gene families. The sunflower genome was found to have 27 SAP genes, distributed across 14 chromosomes. The evolutionary analysis revealed that the SAP family genes could be divided into three subgroups. Notably, the annuus variety exhibited amplification of the SAP gene for Group 3. Among the Compositae species, C. morifolium demonstrated the highest number of collinearity gene pairs and the closest distance on the phylogenetic tree, suggesting relative conservation in the evolutionary process. An analysis of gene structure revealed that Group 1 exhibited the most complex gene structure, while the majority of HaSAP genes in Group 2 and Group 3 lacked introns. The promoter analysis revealed the presence of cis-acting elements related to ABA, indicating their involvement in stress responses. The expression analysis indicated the potential involvement of 10 genes (HaSAP1, HaSAP3, HaSAP8, HaSAP10, HaSAP15, HaSAP16, HaSAP21, HaSAP22, HaSAP23, and HaSAP26) in sunflower salt tolerance. The expression of these 10 genes were then examined under salt and drought stress using qRT-PCR, and the tissue-specific expression patterns of these 10 genes were also analyzed. HaSAP1, HaSAP21, and HaSAP23 exhibited consistent expression patterns under both salt and drought stress, indicating these genes play a role in both salt tolerance and drought resistance in sunflower. The findings of this study highlight the significant contribution of the SAP gene family to salt tolerance and drought resistance in sunflower.

A natural small molecule alleviates liver fibrosis by targeting apolipoprotein L2.

Liver fibrosis is an urgent clinical problem without effective therapies. Here we conducted a high-content screening on a natural Euphorbiaceae diterpenoid library to identify a potent anti-liver fibrosis lead, 12-deoxyphorbol 13-palmitate (DP). Leveraging a photo-affinity labeling approach, apolipoprotein L2 (APOL2), an endoplasmic reticulum (ER)-rich protein, was identified as the direct target of DP. Mechanistically, APOL2 is induced in activated hepatic stellate cells upon transforming growth factor-ß1 (TGF-ß1) stimulation, which then binds to sarcoplasmic/ER calcium ATPase 2 (SERCA2) to trigger ER stress and elevate its downstream protein kinase R-like ER kinase (PERK)-hairy and enhancer of split 1 (HES1) axis, ultimately promoting liver fibrosis. As a result, targeting APOL2 by DP or ablation of APOL2 significantly impairs APOL2-SERCA2-PERK-HES1 signaling and mitigates fibrosis progression. Our findings not only define APOL2 as a novel therapeutic target for liver fibrosis but also highlight DP as a promising lead for treatment of this symptom.