Trophic transfer of antibiotics in the benthic-pelagic coupling foodweb in a macrophyte-dominated shallow lake: The importance of pelagic-benthic coupling strength and baseline organism.

In lake ecosystems, pelagic-benthic coupling strength (PBCS) is closely related to foodweb structure and pollutant transport. However, the trophic transfer of antibiotics in a benthic-pelagic coupling foodweb (BPCFW) and the manner in which PBCS influences the trophic magnification factor (TMFs) of antibiotics is still not well understood in the whole lake. Herein, the trophic transfer behavior of 12 quinolone antibiotics (QNs) in the BPCFW of Baiyangdian Lake were studied during the period of 2018-2019. It was revealed that 24 dominant species were contained in the BPCFW, and the trophic level was 0.42-2.94. Seven QNs were detected in organisms, the detection frequencies of ofloxacin (OFL), flumequine (FLU), norfloxacin (NOR), and enrofloxacin (ENR) were higher than other QNs. The ∑QN concentration in all species was 11.3-321 ng/g dw. The TMFs for ENR and NOR were trophic magnification, while for FLU/OFL it was trophic dilution. The PBCS showed spatial-temporal variation, with a range of 0.6977-0.7910. The TMFs of ENR, FLU, and OFL were significantly positively correlated with PBCS. Phytoplankton and macrophyte biomasses showed indirect impact on the TMFs of QNs by directly influencing the PBCS. Therefore, the PBCS was the direct influencing factor for the TMFs of chemicals.

[Fatal Familial Insomnia With Significant Correlations Between Involuntary Movements and Postural Changes:Report of One Case].

Fatal familial insomnia,an autosomal dominant prion disease,is rare.We reported the clinical symptoms,examination results,diagnosis,treatment,and prognosis of a patient who was diagnosed with fatal familial insomnia.Furthermore,we described the unique clinical manifestations that involuntary movements and laryngeal stridor were significantly correlated with postural changes,aiming to provide reference for the clinical diagnosis,treatment,and research of the disease in the future.

Antibiotic resistance genes and mobile genetic elements in different rivers: The link with antibiotics, microbial communities, and human activities.

Rivers as a critical sink for antibiotic resistance genes (ARGs), and the distribution and spread of ARGs are related to environmental factors, human activities, and biotic factors (e.g. mobile genetic elements (MGEs)). However, the potential link among ARGs, microbial community, and MGEs in rivers under different antibiotic concentration and human activities remains unclear. In this study, 2 urban rivers (URs), 1 rural-urban river (RUR), and 2 rural rivers (RRs) were investigated to identify the spatial-temporal variation and driving force of ARGs. The total concentration of quinolones (QNs) was 160.1-2151 ng·g-1 in URs, 23.34-1188 ng·g-1 in RUR, and 16.39-85.98 ng·g-1 in RRs. Total population (TP), gross domestic production (GDP), sewage, industrial enterprise (IE), and IEGDP appeared significantly spatial difference in URs, RUR, and RRs. In terms of ARGs, 145-161 subtypes were detected in URs, 59-61 subtypes in RURs, and 46-79 subtypes in RRs. For MGEs, 55-60 MGEs subtypes were detected in URs, 29-30 subtypes in RUR, and 29-35 subtypes in RRs. Significantly positive correlation between MGEs and ARGs were found in these rivers. More ARGs subtypes were related to MGEs in URs than those in RUR and RRs. Overall, MGEs and QNs showed significantly direct positive impact on the abundance of ARGs in all rivers, while microbial community was significantly positive impact on the ARGs abundance in URs and RUR. The ARGs abundance in URs/RUR were directly positive influenced by microbial community/MGEs/socioeconomic elements (SEs)/QNs, while those in RRs were directly positive influenced by QNs/MGEs and indirectly positive impacted by SEs. Most QNs resistance risk showed significantly positive correlation with the abundance of ARGs types. Therefore, not only need to consider the concentration of antibiotics, but also should pay more attention to SEs and MGEs in antibiotics risk management and control.

Characteristics of Lactic Acid Bacteria as Potential Probiotic Starters and Their Effects on the Quality of Fermented Sausages.

The aim of this study was to explore the potential of commercial lactic acid bacteria (LAB) as probiotic starters in fermented sausages. We initially investigated the growth activity, acid production capability, and tolerance to fermentation conditions of Lactobacillus sakei, Lactiplantibacillus plantarum, and Pediococcus pentosaceus. All three LAB strains proved viable as starters for fermented sausages. Subsequently, we explored their potential as probiotics based on their antibacterial and antioxidant capabilities. L. plantarum exhibited stronger inhibition against Escherichia coli and Staphylococcus aureus. All three strains displayed antioxidant abilities, with cell-free supernatants showing a higher antioxidant activity compared to intact cells and cell-free extracts. Moreover, the activities of superoxide dismutase, glutathione peroxidase, and catalase were stronger in the cell-free supernatant, cell-free extract, and intact cell, respectively. Finally, we individually and collectively inoculated these three LAB strains into sausages to investigate their impact on quality during the fermentation process. External starters significantly reduced pH, thiobarbituric acid reactive substances, and sodium nitrite levels. The improvements in color and texture had positive effects, with the L. plantarum inoculation achieving higher sensory scores. Overall, all three LAB strains show promise as probiotic fermentation starters in sausage production.

[Source Analysis and Health Risk Assessment of Heavy Metals in the Groundwater of Shijiazhuang, a Typical City in North China Plain].

Increasing attention has been paid to the heavy metal pollution in groundwater. The source analysis and risk assessment of heavy metals will provide data and method support for the targeted control of heavy metal pollution in groundwater. In this study, 20 sampling sites were selected in Shijiazhuang City. The APCS-MLR model and health risk model were applied to analyze and evaluate the pollution sources and health risks of 10 types of heavy metals in the groundwater of Shijiazhuang. The results showed that ① the mean concentration of heavy metals in groundwater followed the order of Fe>Zn>Mn>Cu>Al>Pb>Cr>As>Cd>Hg, and the mean ρ(Fe) and ρ(Pb) were 260.3 µg·L-1 and 10.01 µg·L-1, respectively. According to the results of the single factor and Nemerow index, Pb, Fe, and Cd primarily contributed to the heavy metal pollution in the groundwater. ② The concentration of heavy metals ranged from 47.30 to 2560 µg·L-1. In terms of spatial distribution, the highest concentration appeared at S3 (2560 µg·L-1), whereas the lowest concentration was at S9 (47.30 µg·L-1). ③ Source analysis results showed that industrial and agricultural activities, transportation emission, and geological background were the major heavy metal sources, among which the contribution of industrial and agricultural activities was the highest (47.83%). ④ The industrial-agricultural activities posed a potential threat to adults (HI>1); however, the non-cancer and the cancer risks of other sources for both adults and children were at an acceptable level (HI<1) and potential threat level, respectively; industrial-agricultural activities were the major source of non-cancer (adults:52.46%, children:52.45%) and cancer risks (adults:65.22%, children:65.69%), among which Cd and As showed high cancer risk. Therefore, to ensure the safety of the groundwater environment, strictly controlling the pollution sources and further strengthening the risk control of heavy metal pollution in groundwater are necessary.

[Source Apportionment and Source-specific Risk of Typical Antibiotics in Baiyangdian Lake].

The current situation of antibiotic pollution in lakes is critical. At present, most of the previous studies on antibiotics in lakes have focused on the spatiotemporal distribution and risk assessment, while less attention has been paid to the source apportionment. Ultra-high performance liquid chromatography-mass spectrometry was used to determine the concentration of tetracyclines (TCs), sulfonamides (SAs), and quinolones (QNs) in the samples. The source apportionment and source-specific risk of typical antibiotics in the study area were analyzed using the combination of a PMF model and risk quotients (RQ). The results showed that ① the total concentrations of target antibiotics (Σ antibiotics) ranged from ND to 2635 ng·L-1 for surface water and from ND to 259.8 ng·g-1 for sediments. ② The spatial distribution of QNs in surface water decreased from west to east, SAs decreased from middle to north and south, and TCs increased from middle to north and south. In the sediment, QNs decreased from middle to east and west, whereas SAs and TCs increased from east to west. ③ Aquaculture was the major antibiotic source, accounting for the highest proportion (33.2%), followed by sewage treatment plants (29.2%), livestock activities (18.9%), and domestic sewage (18.7%). ④ The ecological risk assessment results showed that enrofloxacin and flumequine were at a medium-high risk level. ⑤ For the spatial distribution of source-specific risk, the results showed that the aquaculture at S1 was at a high risk level, whereas the source-specific risks for other sites were at a medium-low risk level. In terms of source types, aquaculture was at a medium-high risk level, whereas the other sources were at a medium-low risk level. Therefore, considering the major sources and source-specific risk level of antibiotics, more precise and scientific antibiotic risk control should be adopted in Baiyangdian Lake.

Postoperative fasting plasma glucose and family history diabetes mellitus can predict post-transplantation diabetes mellitus in kidney transplant recipients.

PURPOSE: To explore whether glycated albumin (GA) or fasting plasma glucose (FPG), both routinely monitored during patients' hospital stay, can be used to predict post-transplantation diabetes mellitus (PTDM). METHODS: All kidney transplantation recipients (KTRs) from January 2017 to December 2018 were followed-up for 1 year. PTDM was diagnosed from day 45 post-operation to 1 year. When the completeness was above 80%, FPG or GA data on the day was selected, analyzed, and presented as range parameters and standard deviation (SD) and compared between PTDM and non-PTDM groups in fluctuation and stable periods. The predictive cut-off values were determined via receiver operating characteristic (ROC) analysis. The PTDM combined predictive mode, formed by the independent risk factors derived from logistic regression analyses, was compared with each independent risk factor with the independent ROC curve test. RESULTS: Among 536 KTRs, 38 patients developed PTDM up to 1 year post-operatively. The family history diabetes mellitus (OR, 3.21; P = 0.035), the FPG SD in fluctuation period >2.09 mmol/L (OR, 3.06; P = 0.002), and the FPG maximum in stable period >5.08 mmol/L (OR, 6.85; P < 0.001) were the PTDM independent risk factors. The discrimination of the combined mode (area under the curve = 0.81, sensitivity = 73.68%, and specificity = 76.31%) was higher than each prediction (P < 0.05). CONCLUSIONS: The FPG standard deviation during the fluctuation period, FPG maximum during the stable period, and family history diabetes mellitus predicted PTDM with good discrimination and potential routine clinical use.

Long-term statins administration exacerbates diabetic nephropathy via ectopic fat deposition in diabetic mice.

Statins play an important role in the treatment of diabetic nephropathy. Increasing attention has been given to the relationship between statins and insulin resistance, but many randomized controlled trials confirm that the therapeutic effects of statins on diabetic nephropathy are more beneficial than harmful. However, further confirmation of whether the beneficial effects of chronic statin administration on diabetic nephropathy outweigh the detrimental effects is urgently needed. Here, we find that long-term statin administration may increase insulin resistance, interfere with lipid metabolism, leads to inflammation and fibrosis, and ultimately fuel diabetic nephropathy progression in diabetic mice. Mechanistically, activation of insulin-regulated phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway leads to increased fatty acid synthesis. Furthermore, statins administration increases lipid uptake and inhibits fatty acid oxidation, leading to lipid deposition. Here we show that long-term statins administration exacerbates diabetic nephropathy via ectopic fat deposition in diabetic mice.

Postoperative day 1 serum cystatin C level predicts postoperative delayed graft function after kidney transplantation.

Background: Delayed graft function (DGF) commonly occurs after kidney transplantation, but no clinical predictors for guiding post-transplant management are available. Materials and methods: Data including demographics, surgery, anesthesia, postoperative day 1 serum cystatin C (S-CysC) level, kidney functions, and postoperative complications in 603 kidney transplant recipients who met the enrollment criteria from January 2017 to December 2018 were collected and analyzed to form the Intention-To-Treat (ITT) set. All perioperative data were screened using the least absolute shrinkage and selection operator. The discrimination, calibration, and clinical effectiveness of the predictor were verified with area under curve (AUC), calibration plot, clinical decision curve, and impact curve. The predictor was trained in Per-Protocol set, validated in the ITT set, and its stability was further tested in the bootstrap resample data. Result: Patients with DGF had significantly higher postoperative day 1 S-CysC level (4.2 ± 1.2 vs. 2.8 ± 0.9 mg/L; P < 0.001), serum creatinine level (821.1 ± 301.7 vs. 554.3 ± 223.2 µmol/L; P < 0.001) and dialysis postoperative (74 [82.2%] vs. 25 [5.9%]; P < 0.001) compared with patients without DGF. Among 41 potential predictors, S-CysC was the most effective in the parsimonious model, and its diagnostic cut-off value was 3.80 mg/L with the risk score (OR, 13.45; 95% CI, 8.02-22.57; P < 0.001). Its specificity and sensitivity indicated by AUC was 0.832 (95% CI, 0.779-0.884; P < 0.001) with well fit calibration. S-CysC yielded up to 50% of clinical benefit rate with 1:4 of cost/benefit ratio. Conclusion: The postoperative day 1 S-CysC level predicts DGF and may be used as a predictor of DGF but warrants further study.

Demonstration of an ultra-compact 8-channel sinusoidal silicon waveguide array for optical phased array.

Here we demonstrate an ultra-compact 8-channel sinusoidal silicon waveguide array for an optical phased array. In our device, based on sinusoidal bending, the cross talk (CT) between waveguides can be efficiently reduced with a waveguide pitch of only 695 nm. For the transverse electric (TE) mode, the simulation results show that the insertion loss (IL) of the 100-µm-long device is 0.1 dB and the CT between all waveguides is lower than -25 dB at 1550 nm. In the measurements, an IL of less than 1 dB and CT lower than -18 dB are obtained. Since the pitch is related to the beam-steering range and power consumption of the optical phased array, such an ultra-compact device could potentially be a good candidate to build the emitter for an energy-efficient optical phased array with a large field of view.

Nanotherapeutics Overcoming the Blood-Brain Barrier for Glioblastoma Treatment.

Glioblastoma (GBM) is the most common malignant primary brain tumor with a poor prognosis. The current standard treatment regimen represented by temozolomide/radiotherapy has an average survival time of 14.6 months, while the 5-year survival rate is still less than 5%. New therapeutics are still highly needed to improve the therapeutic outcome of GBM treatment. The blood-brain barrier (BBB) is the main barrier that prevents therapeutic drugs from reaching the brain. Nanotechnologies that enable drug delivery across the BBB hold great promise for the treatment of GBM. This review summarizes various drug delivery systems used to treat glioma and focuses on their approaches for overcoming the BBB to enhance the accumulation of small molecules, protein and gene drugs, etc. in the brain.

Ultra-compact multimode waveguide bend with shallowly etched grooves.

In this work, an ultra-sharp multimode waveguide bend (MWB) based on gradient shallowly etched grooves is proposed and demonstrated. With a bending radius of only 5.6 µm, our shallowly-etched-groove multimode waveguide bend (SMWB) can enable low excess loss and low-crosstalk propagation with the four lowest-order TE mode-channels, simultaneously. In the simulation, the excess losses of the proposed 90°- SMWB for TE0-TE3 are all below 0.46 dB and the inter-mode crosstalks are lower than -18 dB in 1500 nm-1600 nm. Furthermore, the measured results of the fabricated 90°- SMWB show that the excess losses for TE0-TE3 are less than 1 dB and the inter-mode crosstalks are all below -14 dB in 1510 nm-1580 nm. Such a proposed device thus provides a promising solution for ultra-compact MWBs in multimode silicon photonics.

Design of an ultra-compact low-crosstalk sinusoidal silicon waveguide array for optical phased array.

In this work, an ultra-compact low-crosstalk sinusoidal silicon waveguide array is proposed and analyzed. We first design a pair of low-crosstalk sinusoidal silicon waveguides with a pitch of 695 nm, where the sinusoidal bends are the key to reduce the crosstalk between waveguides. Then, based on this idea, we propose a low-crosstalk sinusoidal silicon waveguide array with a 695 nm pitch. The simulation results show that for an array length of 100 µm, the insertion loss is as low as 0.08 dB, and the crosstalk is lower than -26 dB at 1550 nm. The 695 nm pitch waveguide array also exhibits a favorable fabrication error tolerance when taking into account the waveguide width variations in practice. Moreover, within the acceptable range of crosstalk, the center-to-center distance between adjacent waveguides of this array can be further reduced to 615 nm. Since the pitch is related to the power consumption and beam-steering range of the optical phased array, our design provides an effective method to build the emitter for an energy-efficient optical phased array with a large field of view.

Evaluating the scope of intramedullary invasion of malignant bone tumor by DCE-MRI quantitative parameters in animal study.

The purpose was to analyze the value of quantitative parameters of DCE-MRI in evaluating micro-infiltration of malignant bone tumors. METHODS: Thirty-nine New Zealand white rabbits were used to establish malignant bone tumor models by implanting VX2 tumor fragments into the right tibiae. After three weeks, models were examined by conventional MRI and DCE-MRI; then the right tibiae were cut into sagittal sections and partitioned into histology slices for comparison with microscopic findings. Micro-infiltration groups were selected and the range of infiltration was determined under the microscope, and corresponding DCE images analyzed to obtain the quantitative parameters include Ktrans, Kep, ve and vp in parenchyma areas, micro-infiltration areas and simple edema areas. One-way ANOVA was used to compare the differences of the parameters between the three areas. Receiver operating characteristic curves (ROCs) were plotted to determine the accuracy of different parameters by area under curves (AUCs). RESULTS: 22 cases (22/39, 56.4%) were included in the micro-infiltration group and the infiltration depth ranged from 1.3 mm to 4.6 mm, with an average depth of 3.2 mm ± 0.8 mm. The statistical results of quantitative parameters in the three areas were as follows: Ktrans values were (0.494 ± 0.052), (0.403  ±  0.049), (0.173 ± 0.047) min-1 (p = =0.000), Kep values were (1.959 ± 0.65), (1.528 ± 0.372), (1.174 ± 0.486) min-1 (p = =0.000), ve values were (0.247 ± 0.068), (0.283 ± 0.057), (0.168 ± 0.062) min-1 (p = =0.000), vp values were (0.125 ± 0.036), (0.108 ± 0.033), (0.098 ± 0.025) min-1 (p = =0.022), respectively. Ktrans and Kep values had significant difference in the three areas after comparing between-groups, respectively. However, there were no significant difference in vp values between parenchyma and micro-infiltration areas (p = =0.078), micro-infiltration and simple edema areas (p = =0.315), and ve values between parenchyma and micro-infiltration areas (p = =0.056). The ve values were higher in parenchyma and micro-infiltration areas then simple edema areas. Ktrans had highest accuracy in differentiating different areas (AUC > 0.9), respectively. CONCLUSION: Quantitative parameters Ktrans, Kep and ve can assess the extent of intramedullary invasion of malignant bone tumors. Ktrans have highest accuracy in differentiating different regions.

Edema Surrounding Benign Tumors and Tumor-Like Lesions.

OBJECTIVE: To explore the incidence and significance of intra- and extra-osseous edema associated with benign tumors and tumor-like diseases. METHODS: Magnetic resonance imaging (MRI) data from 300 benign osseous tumors and tumor-like diseases diagnosed by pathology were retrospectively reviewed. Borderline tumors, cases associated with pathological fractures, and skull lesions were excluded from the study. Bone marrow and soft tissue edema were defined on T2WI with fat suppression on MRI in all cases. The incidence rate of edema in benign tumors and tumor-like diseases was determined using the χ 2 test. The preoperative diagnoses were reviewed, and the effect of edema on the differential diagnosis of benign and malignant tumors was analyzed. RESULTS: The incidence rate of bone marrow and soft tissue edema associated with benign tumors and tumor-like diseases was 35.7% (107/300), including 84.4% (27/32) Langerhans cell histiocytosis, 86.4% (19/22) osteoblastoma, 93.9% (31/33) osteoid osteoma, and 85.2% (23/27) chondroblastoma cases. There was no statistically significant difference in the incidence of edema among the four diseases (χ 2 = 1.7, P > 0.05). Of 107 cases associated with edema, 49 (45.8%) were misdiagnosed as malignant tumors by MRI preoperatively. CONCLUSION: Bone marrow and soft tissue edema are a common finding associated with benign bone tumors and tumor-like diseases, and they are frequently detected in Langerhans cell histiocytosis, osteoblastoma, osteoid osteoma, and chondroblastoma.

Nanomechanical Characterization of Vertical Nanopillars Using an MEMS-SPM Nano-Bending Testing Platform.

Nanomechanical characterization of vertically aligned micro- and nanopillars plays an important role in quality control of pillar-based sensors and devices. A microelectromechanical system based scanning probe microscope (MEMS-SPM) has been developed for quantitative measurement of the bending stiffness of micro- and nanopillars with high aspect ratios. The MEMS-SPM exhibits large in-plane displacement with subnanometric resolution and medium probing force beyond 100 micro-Newtons. A proof-of-principle experimental setup using an MEMS-SPM prototype has been built to experimentally determine the in-plane bending stiffness of silicon nanopillars with an aspect ratio higher than 10. Comparison between the experimental results and the analytical and FEM evaluation has been demonstrated. Measurement uncertainty analysis indicates that this nano-bending system is able to determine the pillar bending stiffness with an uncertainty better than 5%, provided that the pillars' stiffness is close to the suspending stiffness of the MEMS-SPM. The MEMS-SPM measurement setup is capable of on-chip quantitative nanomechanical characterization of pillar-like nano-objects fabricated out of different materials.

Study on the spectrum-effect relationship of the xanthine oxidase inhibitory activity of Ligustrum lucidum.

To evaluate the xanthine oxidase inhibitory activity of the chemical constituents of Ligustrum lucidum in vitro, the spectrum-effect relationship was investigated. The high-performance liquid chromatography fingerprint was established by ultraviolet spectrophotometry, and the xanthine oxidase inhibitory activity was tested in vitro by a high-throughput screening method. Cluster analysis, principal component analysis, gray correlation analysis, and partial least squares regression were used to explore the spectrum-effect relationships. Sixty batches of Ligustrum lucidum were collected from 16 provinces for testing. The results revealed differences among the batches of medicinal materials, and the similarity score was between 0.635 and 0.968. Thirty-three characteristic peaks (1-33) were calibrated by fingerprint evaluation software for traditional Chinese medicine. The spectrum-effect relationship study further revealed that the contents of peaks 1, 2, 4, 5, 6, 7, 14, 17, 25, 28, 31, and 33, which are potentially critical ingredients for quality control of Ligustrum lucidum fruit, were highly correlated with the inhibition of xanthine oxidase activity.

Core-Shell CoNi@Graphitic Carbon Decorated on B,N-Codoped Hollow Carbon Polyhedrons toward Lightweight and High-Efficiency Microwave Attenuation.

Lightweight and high-efficiency microwave attenuation are two major challenges in the exploration of carbon-based absorbers, which can be achieved simultaneously by manipulating their chemical composition, microstructure, or impedance matching. In this work, core-shell CoNi@graphitic carbon decorated on B,N-codoped hollow carbon polyhedrons has been constructed by a facile pyrolysis process using metal-organic frameworks as precursors. The B,N-codoped hollow carbon polyhedrons, originated from the calcination of Co-Ni-ZIF-67, are composed of carbon nanocages and BN domains, and CoNi alloy is encapsulated by graphitic carbon layers. With a filling loading of 30 wt %, the absorber exhibits a maximum RL of -62.8 dB at 7.2 GHz with 3 mm and the effective absorption bandwidth below -10 dB remarkably reaches as strong as 8 GHz when the thickness is only 2 mm. The outstanding microwave absorption performance stems from the hollow carbon polyhedrons and carbon nanocages with interior cavities, the synergistic coupling effect between the abundant B-C-N heteroatoms, the strong dipolar/interfacial polarizations, the multiple scatterings, and the improved impedance matching. This study demonstrates that the codoped strategy provides a new way for the rational design of carbon-based absorbers with lightweight and superior microwave attenuation.

Loss of pigment epithelium-derived factor leads to ovarian oxidative damage accompanied by diminished ovarian reserve in mice.

AIMS: This study aims to investigate the pathophysiological role and mechanism of pigment epithelium-derived factor (PEDF) deletion in ovarian damage. METHODS: Female PEDF-knockout mice and their wild-type littermates were used in this study. Relevant tests were performed at 8-10 weeks or 32 weeks of age. KEY FINDINGS: Compared to the wild-type mice, the PEDF-knockout mice showed diminished ovarian reserve (DOR), worse ovum quality after injection to induce controlled ovarian stimulation, increased serum follicle stimulating hormone (FSH) level and an follicle stimulating hormone/luteinizing hormone (FSH/LH) ratio. Moreover, severe ovarian oxidative damage was found in ovaries of PEDF-knockout mice that mainly manifested as an accumulation of reactive oxygen species (ROS), NF­E2-related factor 2 (Nrf2) pathway activation, significantly upregulated expression of ROS-generating genes. Correspondingly, the PEDF-knockout mice exhibited lipid metabolism disorder and insulin resistance, which mainly manifested as obesity, abdominal fat accumulation, adipocyte enlargement, severe ectopic fat deposition, dyslipidemia, changes in adipokine levels, hyperglycemia, hyperinsulinemia, impaired glucose tolerance, impaired insulin tolerance and significantly declined protein kinase B (Akt) phosphorylation levels. SIGNIFICANCE: Loss of PEDF leads to ovarian oxidative damage accompanied by DOR in mice, this is related to PEDF deficiency induced severe insulin resistance and lipid metabolism disorder. Therefore, PEDF may be a potential target for the treatment of diseases related to ovarian oxidative damage.