Intestinal epithelial dopamine receptor signaling drives sex-specific disease exacerbation in a mouse model of multiple sclerosis.

Although the gut microbiota can influence central nervous system (CNS) autoimmune diseases, the contribution of the intestinal epithelium to CNS autoimmunity is less clear. Here, we showed that intestinal epithelial dopamine D2 receptors (IEC DRD2) promoted sex-specific disease progression in an animal model of multiple sclerosis. Female mice lacking Drd2 selectively in intestinal epithelial cells showed a blunted inflammatory response in the CNS and reduced disease progression. In contrast, overexpression or activation of IEC DRD2 by phenylethylamine administration exacerbated disease severity. This was accompanied by altered lysozyme expression and gut microbiota composition, including reduced abundance of Lactobacillus species. Furthermore, treatment with N2-acetyl-L-lysine, a metabolite derived from Lactobacillus, suppressed microglial activation and neurodegeneration. Taken together, our study indicates that IEC DRD2 hyperactivity impacts gut microbial abundances and increases susceptibility to CNS autoimmune diseases in a female-biased manner, opening up future avenues for sex-specific interventions of CNS autoimmune diseases.

Magnetically powered microwheel thrombolysis of occlusive thrombi in zebrafish.

Tissue plasminogen activator (tPA) is the only FDA-approved treatment for ischemic stroke but carries significant risks, including major hemorrhage. Additional options are needed, especially in small vessel thrombi which account for ~25% of ischemic strokes. We have previously shown that tPA-functionalized colloidal microparticles can be assembled into microwheels (µwheels) and manipulated under the control of applied magnetic fields to enable rapid thrombolysis of fibrin gels in microfluidic models of thrombosis. Transparent zebrafish larvae have a highly conserved coagulation cascade that enables studies of hemostasis and thrombosis in the context of intact vasculature, clotting factors, and blood cells. Here, we show that tPA-functionalized µwheels can perform rapid and targeted recanalization in vivo. This effect requires both tPA and µwheels, as minimal to no recanalization is achieved with tPA alone, µwheels alone, or tPA-functionalized microparticles in the absence of a magnetic field. We evaluated tPA-functionalized µwheels in CRISPR-generated plasminogen (plg) heterozygous and homozygous mutants and confirmed that tPA-functionalized µwheels are dose-dependent on plasminogen for lysis. We have found that magnetically powered µwheels as a targeted tPA delivery system are dramatically more efficient at plasmin-mediated thrombolysis than systemic delivery in vivo. Further development of this system in fish and mammalian models could enable a less invasive strategy for alleviating ischemia that is safer than directed thrombectomy or systemic infusion of tPA.

Generation of superposed orbital angular momentum beams using a free-electron laser oscillator.

With wavelength tunability, free-electron lasers (FELs) are well-suited for generating orbital angular momentum (OAM) beams in a wide photon energy range. We report here the first experimental demonstration of OAM beam generation using an oscillator FEL with the tens of picosecond pulse duration. Lasing around 458 nm, we have produced the four lowest orders of superposed Laguerre-Gaussian beams using a very long FEL resonator of 53.73 m. The produced beams have good beam quality, excellent stability, and substantial average power. We have also developed a pulsed operation mode for these beams with a highly reproducible temporal structure for a range of repetition rate of 1-30 Hz. This development can be extended to short wavelengths, for example to x-rays using a future x-ray FEL oscillator. The OAM operation of such a storage-ring FEL also paves the way for the generation of OAM gamma-ray beams via inverse Compton scattering.

Integrated profiling identifies DXS253E as a potential prognostic marker in colorectal cancer.

BACKGROUND: Increasing evidence suggests that DXS253E is critical for cancer development and progression, but the function and potential mechanism of DXS253E in colorectal cancer (CRC) remain largely unknown. In this study, we evaluated the clinical significance and explored the underlying mechanism of DXS253E in CRC. METHODS: DXS253E expression in cancer tissues was investigated using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The Kaplan-Meier plot was used to assess the prognosis of DXS253E. The cBioPortal, MethSurv, and Tumor Immune Estimation Resource (TIMER) databases were employed to analyze the mutation profile, methylation, and immune infiltration associated with DXS253E. The biological functions of DXS253E in CRC cells were determined by CCK-8 assay, plate cloning assay, Transwell assay, flow cytometry, lactate assay, western blot, and qRT-PCR. RESULTS: DXS253E was upregulated in CRC tissues and high DXS253E expression levels were correlated with poor survival in CRC patients. Our bioinformatics analyses showed that high DXS253E gene methylation levels were associated with the favorable prognosis of CRC patients. Furthermore, DXS253E levels were linked to the expression levels of several immunomodulatory genes and an abundance of immune cells. Mechanistically, the overexpression of DXS253E enhanced proliferation, migration, invasion, and the aerobic glycolysis of CRC cells through the AKT/mTOR pathway. CONCLUSIONS: We demonstrated that DXS253E functions as a potential role in CRC progression and may serve as an indicator of outcomes and a therapeutic target for regulating the AKT/mTOR pathway in CRC.

Acute lung injury: a view from the perspective of necroptosis.

BACKGROUND: ALI/ARDS is a syndrome of acute onset characterized by progressive hypoxemia and noncardiogenic pulmonary edema as the primary clinical manifestations. Necroptosis is a form of programmed cell necrosis that is precisely regulated by molecular signals. This process is characterized by organelle swelling and membrane rupture, is highly immunogenic, involves extensive crosstalk with various cellular stress mechanisms, and is significantly implicated in the onset and progression of ALI/ARDS. METHODS: The current body of literature on necroptosis and ALI/ARDS was thoroughly reviewed. Initially, an overview of the molecular mechanism of necroptosis was provided, followed by an examination of its interactions with apoptosis, pyroptosis, autophagy, ferroptosis, PANOptosis, and NETosis. Subsequently, the involvement of necroptosis in various stages of ALI/ARDS progression was delineated. Lastly, drugs targeting necroptosis, biomarkers, and current obstacles were presented. CONCLUSION: Necroptosis plays an important role in the progression of ALI/ARDS. However, since ALI/ARDS is a clinical syndrome caused by a variety of mechanisms, we emphasize that while focusing on necroptosis, it may be more beneficial to treat ALI/ARDS by collaborating with other mechanisms.

Vestigial mediates the effect of insulin signaling pathway on wing-morph switching in planthoppers.

Wing polymorphism is an evolutionary feature found in a wide variety of insects, which offers a model system for studying the evolutionary significance of dispersal. In the wing-dimorphic planthopper Nilaparvata lugens, the insulin/insulin-like growth factor signaling (IIS) pathway acts as a 'master signal' that directs the development of either long-winged (LW) or short-winged (SW) morphs via regulation of the activity of Forkhead transcription factor subgroup O (NlFoxO). However, downstream effectors of the IIS-FoxO signaling cascade that mediate alternative wing morphs are unclear. Here we found that vestigial (Nlvg), a key wing-patterning gene, is selectively and temporally regulated by the IIS-FoxO signaling cascade during the wing-morph decision stage (fifth-instar stage). RNA interference (RNAi)-mediated silencing of Nlfoxo increase Nlvg expression in the fifth-instar stage (the last nymphal stage), thereby inducing LW development. Conversely, silencing of Nlvg can antagonize the effects of IIS activity on LW development, redirecting wing commitment from LW to the morph with intermediate wing size. In vitro and in vivo binding assays indicated that NlFoxO protein may suppress Nlvg expression by directly binding to the first intron region of the Nlvg locus. Our findings provide a first glimpse of the link connecting the IIS pathway to the wing-patterning network on the developmental plasticity of wings in insects, and help us understanding how phenotypic diversity is generated by the modification of a common set of pattern elements.

Tandem Mass Tag-Based Proteomic Profiling Identifies Biomarkers in Drainage Fluid for Early Detection of Anastomotic Leakage after Rectal Cancer Resection.

Anastomotic leakage (AL), one of the most severe complications in rectal surgery, is often diagnosed late because of the low specificity of the clinical symptoms and limitations of current clinical investigations. Identification of patients with early AL remains challenging. Here, we explored the protein expression profiles of AL patients to provide potential biomarkers to identify AL in patients who undergo surgery for rectal cancer. We screened differentially expressed proteins (DEPs) in drainage fluid from AL and non-AL patients using a tandem mass tag method. A total of 248 DEPs, including 98 upregulated and 150 downregulated proteins, were identified between AL and non-AL groups. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that DEPs were enriched in neutrophil degranulation, bacterial infection, proteolysis, hemostasis, and complement and coagulation cascades. The results of enzyme-linked immunosorbent assay validated that the expression of the top three upregulated DEPs, AMY2A, RETN, and CELA3A, was significantly increased in the drainage fluid of AL patients, compared with that of non-AL patients (AMY2A, P = 0.001; RETN, P < 0.0001; and CELA3A, P = 0.023). Thus, our findings provide several potential biomarkers for the early diagnosis of AL after rectal cancer resection.

High beam quality yellow laser at 588†nm by an intracavity frequency-doubled composite Nd:YVO4 Raman laser.

High beam quality 588 nm radiation was realized based on a frequency-doubled crystalline Raman laser. The bonding crystal of YVO4/Nd:YVO4/YVO4 was used as the laser gain medium, which can accelerate the thermal diffusion. The intracavity Raman conversion and the second harmonic generation were realized by a YVO4 crystal and an LBO crystal, respectively. Under an incident pump power of 49.2 W and a pulse repetition frequency of 50 kHz, the 588 nm power of 2.85 W was obtained with a pulse duration of 3 ns, corresponding to a diode-to-yellow laser conversion efficiency of 5.75% and a slope efficiency of 7.6%. Meanwhile, a single pulse's pulse energy and peak power were 57 µJ and 19 kW, respectively. The severe thermal effects of the self-Raman structure were overcome in the V-shaped cavity, which has excellent mode matching, and combined with the self-cleaning effect of `Raman scattering, the beam quality factor M2 was effectively improved, which was measured optimally to be Mx 2 = 1.207, and My 2 = 1.200, with the incident pump power being 49.2 W.

Image distortion by ambiguous multiple-photon detections in a superconducting nanowire single-photon imager and the correction method.

Scaling up superconducting nanowire single-photon detectors (SNSPDs) into a large array for imaging applications is the current pursuit. Although various readout architectures have been proposed, they cannot resolve multiple-photon detections (MPDs) currently, which limits the operation of the SNSPD arrays at high photon flux. In this study, we focused on the readout ambiguity of a superconducting nanowire single-photon imager applying time-of-flight multiplexing readout. The results showed that image distortion depended on both the incident photon flux and the imaging object. By extracting multiple-photon detections on idle pixels, which were virtual because of the incorrect mapping from the ambiguous readout, a correction method was proposed. An improvement factor of 1.3~9.3 at a photon flux of µ = 5 photon/pulse was obtained, which indicated that joint development of the pixel design and restoration algorithm could compensate for the readout ambiguity and increase the dynamic range.

Bergenin ameliorates diabetic nephropathy in C57BL/6 J mice by TLR4/MyD88/NF-κB signalling pathway regulation.

Bergenin (BG) is a polyphenolic substance which has therapeutic potential in the treatment of diabetic nephropathy (DN), a common complication of type II diabetes. However, the mechanisms underlying these effects remain unclear. We studied the protective effects and mechanisms of BG in DN mice, focusing on the TLR4/MyD88/NF-κB signalling pathway. C57BL/6 J mice were used as experiments (n=60), and 10 animals were randomly selected as normal control. The DN model was developed by administering an intraperitoneal injection of streptozotocin (40 mg/kg BW for three days) and a high-fat diet (n=50). BG (20, 40, and 80 mg/kg BW, once a day) was administered orally for four weeks. After BG treatment, the food and water intake of DN mice decreased, blood glucose levels decreased, and insulin resistance reduced. As a result, serum LDL-C, TC, and TG levels decreased; HDL-C levels increased; SOD, CAT, and GSH-Px levels decreased; and MDA levels increased. BG administration reduced AST, ALT, BUN, and CRE levels and inflammatory factors (including TNF-α, MCP-1, IL-1ß, and IL-6). Histopathology revealed a significant improvement in pathological damage to the liver, kidney, and spleen of mice treated with BG, and TLR4, MyD88, and NF-κB p65 were down-regulated at both mRNA and protein levels in the BG-treated group. Based on these results, BG therapeutic type II DN by hypoglycaemia, improving liver and kidney function, and anti-oxidative stress; reducing inflammation; and inhibiting the TLR4/MyD88/NF-κB signalling pathway. The results of this study suggest that BG can be used as an effective treatment for type II DN.

Protein Labeling Facilitates the Understanding of Protein Corona Formation via Fluorescence Resonance Energy Transfer and Fluorescence Correlation Spectroscopy.

Once nanoparticles enter into the biological milieu, nanoparticle-biomacromolecule complexes, especially the protein corona, swiftly form, which cause obvious effects on the physicochemical properties of both nanoparticles and proteins. Here, the thermodynamic parameters of the interactions between water-soluble GSH-CdSe/ZnS core/shell quantum dots (GSH-QDs) and human serum albumin (HSA) were investigated with the aid of labeling fluorescence of HSA. It was proved that the labeling fluorescence originating from a fluorophore (BDP-CN for instance) could be used to investigate the interactions between QDs and HSA. Gel electrophoresis displayed that the binding ratio between HSA and QDs was ∼2:1 by direct visualization. Fluorescence resonance energy transfer (FRET) results indicated that the distance between the QDs and the fluorophore BDP-CN in HSA was 7.2 nm, which indicated that the distance from the fluorophore to the surface of the QDs was ∼4.8 nm. Fluorescence correlation spectroscopy (FCS) results showed that HSA formed a monolayer of a protein corona with a thickness of 5.5 nm. According to the spatial structure of HSA, we could speculate that the binding site of QDs was located at the side edge (not the triangular plane) of HSA with an equilateral triangular prism. The elaboration of the thermodynamic parameters, binding ratio, and interaction orientation will highly improve the fundamental understanding of the formation of protein corona. This work has guiding significance for the exploration of the interactions between proteins and nanomaterials.

Risk stratification of gallbladder masses by machine learning-based ultrasound radiomics models: a prospective and multi-institutional study.

OBJECTIVE: This study aimed to evaluate the diagnostic performance of machine learning (ML)-based ultrasound (US) radiomics models for risk stratification of gallbladder (GB) masses. METHODS: We prospectively examined 640 pathologically confirmed GB masses obtained from 640 patients between August 2019 and October 2022 at four institutions. Radiomics features were extracted from grayscale US images and germane features were selected. Subsequently, 11 ML algorithms were separately used with the selected features to construct optimum US radiomics models for risk stratification of the GB masses. Furthermore, we compared the diagnostic performance of these models with the conventional US and contrast-enhanced US (CEUS) models. RESULTS: The optimal XGBoost-based US radiomics model for discriminating neoplastic from non-neoplastic GB lesions showed higher diagnostic performance in terms of areas under the curves (AUCs) than the conventional US model (0.822-0.853 vs. 0.642-0.706, p < 0.05) and potentially decreased unnecessary cholecystectomy rate in a speculative comparison with performing cholecystectomy for lesions sized over 10 mm (2.7-13.8% vs. 53.6-64.9%, p < 0.05) in the validation and test sets. The AUCs of the XGBoost-based US radiomics model for discriminating carcinomas from benign GB lesions were higher than the conventional US model (0.904-0.979 vs. 0.706-0.766, p < 0.05). The XGBoost-US radiomics model performed better than the CEUS model in discriminating GB carcinomas (AUC: 0.995 vs. 0.902, p = 0.011). CONCLUSIONS: The proposed ML-based US radiomics models possess the potential capacity for risk stratification of GB masses and may reduce the unnecessary cholecystectomy rate and use of CEUS. CLINICAL RELEVANCE STATEMENT: The machine learning-based ultrasound radiomics models have potential for risk stratification of gallbladder masses and may potentially reduce unnecessary cholecystectomies. KEY POINTS: • The XGBoost-based US radiomics models are useful for the risk stratification of GB masses. • The XGBoost-based US radiomics model is superior to the conventional US model for discriminating neoplastic from non-neoplastic GB lesions and may potentially decrease unnecessary cholecystectomy rate for lesions sized over 10 mm in comparison with the current consensus guideline. • The XGBoost-based US radiomics model could overmatch CEUS model in discriminating GB carcinomas from benign GB lesions.

Bright InP Quantum Dots by Mid-Synthetic Modification with Zinc Halides.

InP quantum dots (QDs) attract growing interest in recent years, owing to their environmental advantages upon applications in display and lighting. However, compared to Cd-based QDs and Pb-based perovskites, the synthesis of InP QDs with high optical quality is relatively more difficult. Here, we established a mid-synthetic modification approach to improve the optical properties of InP-based QDs. Tris(dimethylamino)phosphine ((DMA)3P) and indium iodide were used to prepare InP QDs with a green emission (∼527 nm). By introducing zinc halides (ZnX2) during the mid-synthetic process, the photoluminescence quantum yield (PLQY) of the resulting InP/ZnSeS/ZnS core/shell/shell QDs was increased to >70%, and the full-width-at-half-maximum (FWHM) could be narrowed to ∼40 nm. Transmission electron microscopy clearly showed the improvement of the QDs particle size distribution after introducing ZnX2. It was speculated that ZnX2 was bound to the surface of QDs as a Z-type ligand, which not only passivated surface defects and suppressed the emission of defect states but also prevented Ostwald ripening. The InP cores were also activated by ZnX2, which made the growth of the ZnSeS shell more favorable. The photoluminescence properties started to be improved significantly only when the amount of ZnX2 exceeded 0.5 mmol. As the amount increased, more ZnX2 was distributed around the QDs to form a ligand layer, which prevented the shell precursor from crossing the ligand layer to the surface of the InP core, thus reducing the size of the InP/ZnSeS/ZnS QDs. This work revealed a new role of ZnX2 and found a method for InP QDs with high brightness and low FWHM by the mid-synthetic modification, which would inspire the synthesis of even better InP QDs.

Probabilistic Energy-to-Amplitude Mapping in a Tapered Superconducting Nanowire Single-Photon Detector.

A spectrum-resolved photon detector is crucial for cutting-edge quantum optics, astronomical observation, and spectroscopic sensing. However, such an ability is rarely obtained because a direct linear conversion from weak single-photon energy to a readable electrical signal above the noise level without causing an avalanche is challenging. Here, we overcame these difficulties by building a probabilistic energy-to-amplitude mapping in a tapered superconducting nanowire single-photon detector and combining a computational reconstruction to obtain equivalent spectral resolving capacity. Distinguished dependence of pulse amplitude distributions on varied input spectra has been observed experimentally. As the energy-to-amplitude mapping is probabilistic, statistical measurements are required. By collecting around a few hundred photons, we have demonstrated wavelength perception over a wide spectral range from 600 to 1700 nm with a resolution of 100 nm. These findings represent a new approach to designing spectrum-sensitive SNSPDs for low-light spectroscopic applications.

A two-dimensional analytical model for heavy metal contaminants transport in permeable reactive barrier.

Permeable reactive barrier (PRB) remediation technology has been widely used in the remediation of groundwater contamination. In numerical simulations, neglecting the non-uniform distribution of heavy metal contamination along the depth may lead to deviations between simulation results and reality. The distribution of heavy metals in the soil layer around a non-ferrous mining area in Hezhou, Guangxi, southern China was investigated, and it was found that the standard Gaussian function could well describe the non-uniform distribution of heavy metals in the soil layer. A two-dimensional analytical model solved by the finite element method was used to simulate the migration process of heavy metal contamination in the aquifer and PRB. The results show that the uniform distribution of contaminants along the depth ignores the dilution effect, which may underestimate the service life of the PRB and lead to an overly conservative design of the PRB. The breakthrough time of the PRB decreases with the increase of the maximum initial concentration (Cin,max) and the high concentration range (σ), and increases almost linearly with the barrier thickness (Lw). An optimal design method for PRB location and thickness is proposed, which can provide a reference for the engineering application of PRB.

The hepatoprotective effect of Sophora viciifolia fruit extract against acetaminophen-induced liver injury in mice.

This research demonstrated the protective effect and possible mechanism of the Sophora viciifolia extract (SVE) against acetaminophen-induced liver injury in mice. The levels of ALT and AST in the serum and antioxidant enzyme activity in the liver were measured. We used immunohistochemistry to detect CYP2E1, Nrf2, and Keap1 protein expression in the liver. The mRNA expression in the liver of TNF-α, NF-κB, and IL-6, Nrf2 and its downstream genes HO-1 and GCLC were measured by qRT-PCR. We found that SVE could decrease the ALT and AST levels, promote the activities of SOD, CAT, GSH-Px, and GSH, and ameliorate pathological liver lesions. SVE could down-regulate the mRNA expression of inflammatory factors and up-regulate Nrf2, HO-1 and GCLC. SVE reduced the protein expression of the CYP2E1 and increased the Nrf2 and Keap1. SVE has been shown to have a protective effect against APAP-induced liver injury, possibly through activation of the Keap1-Nrf2 pathway.

[Application of high-speed counter current chromatography in extraction and separation of alkaloids in natural products].

Alkaloids, widespread in plants, have a series of pharmacological activities and have been widely used to treat various diseases. Because alkaloids are usually presented in multicomponent mixtures and are deeply low in content, they are very difficult to extract and separate by traditional methods. High-speed counter current chromatography(HSCCC) is a kind of liquid-liquid chromatography without solid support phase, which has the advantages of large injection volume, low cost, and no irreversible adsorption. Compared with the traditional methods of extraction and separation of alkaloids, HSCCC can ensure the separation of many different alkaloids at one time, with a high recovery and large amount. In this paper, the advantages and disadvantages of HSCCC compared with traditional separation methods were discussed and the solvent system and elution mode of HSCCC used to separate alkaloids in recent years were summarized by referring to the relevant literature to provide some references for the separation of alkaloids by HSCCC.

64-Pixel Mo80Si20 superconducting nanowire single-photon imager with a saturated internal quantum efficiency at 1.5 µm.

A superconducting nanowire single-photon imager (SNSPI) uses a time-multiplexing method to reduce the readout complexity. However, due to the serial connection, the nanowire should be uniform so that a common bias can set all segments of the nanowire to their maximum detection efficiency, which becomes more challenging as the scalability (i.e., the length of the nanowire) increases. Here, we have developed a 64-pixel SNSPI based on amorphous Mo80Si20 film, which yielded a uniform nanowire and slow transmission line. Adjacent detectors were separated by delay lines, giving an imaging field of 270 µm × 240 µm. Benefiting from the high kinetic inductance of Mo80Si20 films, the delay line gave a phase velocity as low as 4.6 µm/ps. The positions of all pixels can be read out with a negligible electrical cross talk of 0.02% by using cryogenic amplifiers. The timing jitter was 100.8 ps. Saturated internal quantum efficiency was observed at a wavelength of 1550 nm. These results demonstrate that amorphous film is a promising material for achieving SNSPIs with large scalability and high efficiency.

Similarities and differences between internet gaming disorder and tobacco use disorder: A large-scale network study.

Studies have shown that internet gaming disorder (IGD) has the potential to be a type of addiction; however, direct comparisons (similarities and differences) between IGD and traditional addictions remain scarce, especially at the neuroimaging level. Resting-state functional magnetic resonance imaging (fMRI) data were collected from 92 individuals with IGD, 96 individuals with tobacco use disorders (TUDs) and 107 individuals who served as healthy controls (HCs). Independent component analysis (ICA) was performed to explore the similarities and differences among these three groups; Granger causality analysis (GCA) was further performed based on the ICA results to determine potential neural features underlying the differences and similarities among the groups. The ICA results indicated significant differences in the subcortical network and cerebellar network. GCA results found that significant differences in bilateral caudate among three groups, and the efferents of dorsal frontostriatal circuit showed significant differences in insula among three groups, whereas efferents of ventral frontostriatal circuit showed significant differences in the medial prefrontal cortex (mPFC). Two kinds of addiction showed differences in thalamus and frontostriatal circuits, and similar changes found in cerebellum and mPFC regions. It suggested that addiction disorders have psychopathology features, and the craving and reward dysfunctions may be the key reasons. Although both substance addiction and behaviour addiction showed craving dysfunction in cerebellum, however, the key reward dysfunction of substance addiction was found in subcortical regions, whereas behaviour addiction located in cortical regions.

EPA-Enriched Phospholipids Alleviate Renal Interstitial Fibrosis in Spontaneously Hypertensive Rats by Regulating TGF-ß Signaling Pathways.

Hypertensive nephropathy is a chronic kidney disease caused by hypertension. Eicosapentaenoic acid (EPA) has been reported to possess an antihypertensive effect, and our previous study suggested that EPA-enriched phospholipid (EPA-PL) had more significant bioactivities compared with traditional EPA. However, the effect of dietary EPA-PL on hypertensive nephropathy has not been studied. The current study was designed to examine the protection of EPA-PL against kidney damage in spontaneously hypertensive rats (SHRs). Treatment with EPA-PL for three weeks significantly reduced blood pressure through regulating the renin-angiotensin system in SHRs. Moreover, dietary EPA-PL distinctly alleviated kidney dysfunction in SHRs, evidenced by reduced plasma creatinine, blood urea nitrogen, and 24 h proteinuria. Histology results revealed that treatment of SHRs with EPA-PL alleviated renal injury and reduced tubulointerstitial fibrosis. Further mechanistic studies indicated that dietary EPA-PL remarkably inhibited the activation of TGF-ß and Smad 3, elevated the phosphorylation level of PI3K/AKT, suppressed the activation of NF-κB, reduced the expression of pro-inflammatory cytokines, including IL-1ß and IL-6, and repressed the oxidative stress and the mitochondria-mediated apoptotic signaling pathway in the kidney. These results indicate that EPA-PL has potential value in the prevention and alleviation of hypertensive nephropathy.