Fatty acid oxidation (FAO) dysfunction is one of the important mechanisms of renal fibrosis. Sirtuin 3 (Sirt3) has been confirmed to alleviate acute kidney injury (AKI) by improving mitochondrial ...function and participate in the regulation of FAO in other disease models. However, it is not clear whether Sirt3 is involved in regulating FAO to improve the prognosis of AKI induced by cisplatin. Here, using a murine model of cisplatin‐induced AKI, we revealed that there were significantly FAO dysfunction and extensive lipid deposition in the mice with AKI. Metabolomics analysis suggested reprogrammed energy metabolism and decreased ATP production. In addition, fatty acid deposition can increase reactive oxygen species (ROS) production and induce apoptosis. Our data suggested that Sirt3 deletion aggravated FAO dysfunction, resulting in increased apoptosis of kidney tissues and aggravated renal injury. The activation of Sirt3 by honokiol could improve FAO and renal function and reduced fatty acid deposition in wide‐type mice, but not Sirt3‐defective mice. We concluded that Sirt3 may regulate FAO by deacetylating liver kinase B1 and activating AMP‐activated protein kinase. Also, the activation of Sirt3 by honokiol increased ATP production as well as reduced ROS and lipid peroxidation through improving mitochondrial function. Collectively, these results provide new evidence that Sirt3 is protective against AKI. Enhancing Sirt3 to improve FAO may be a potential strategy to prevent kidney injury in the future.
Idiopathic pulmonary fibrosis (IPF) is a severe form of lung fibrosis with a high mortality rate. However, the etiology of IPF remains unknown. Here, we report that alterations in lung microbiota ...critically promote pulmonary fibrosis pathogenesis. We found that lung microbiota was dysregulated, and the dysregulated microbiota in turn induced production of interleukin-17B (IL-17B) during bleomycin-induced mouse lung fibrosis. Either lung-microbiota depletion or IL-17B deficiency ameliorated the disease progression. IL-17B cooperated with tumor necrosis factor-α to induce expression of neutrophil-recruiting genes and T helper 17 (Th17)-cell-promoting genes. Three pulmonary commensal microbes, which belong to the genera Bacteroides and Prevotella, were identified to promote fibrotic pathogenesis through IL-17R signaling. We further defined that the outer membrane vesicles (OMVs) that were derived from the identified commensal microbes induced IL-17B production through Toll-like receptor-Myd88 adaptor signaling. Together our data demonstrate that specific pulmonary symbiotic commensals can promote lung fibrosis by regulating a profibrotic inflammatory cytokine network.
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•Alterations in lung microbiota critically promote pulmonary fibrosis•Lung-microbiota-driven IL-17B is critical for pulmonary fibrosis•Three OMV-producing pulmonary microbes are identified to promote lung fibrosis•The microbe-derived OMVs induce IL-17B production through TLR-Myd88 signaling
Although gut microbiota plays critical roles in regulating immunological responses in intestines, the potential roles of lung microbiota in local immune responses are largely unknown. Yang et al. demonstrate that dysregulated lung commensal bacteria drive interleukin-17B production to promote pulmonary inflammation and fibrosis through their outer membrane vesicles.
Seru Production is widely used in the Japanese electronics industry owing to its benefits. The total tardiness can be significantly reduced by Seru Production. We focus on investigating the ...fundamental principle of the total tardiness reduction brought by Seru Production. We formulate the seru system operation with minimising the total tardiness and analyse the solution space. We clarify that the model is non-linear. To exactly obtain the optimal solution of the non-linear model, we decompose the non-linear model into seru formation and seru scheduling which is formulated as a linear model. Thus, the small-scale seru system operation with minimising the total tardiness is solved exactly. For the large-scale problems, we propose a cooperative coevolution algorithm, where two evolution algorithms deal with the seru formation and seru scheduling. In the coevolution process, the two algorithms perform cooperation to seek the better solutions of seru system operation with minimising the total tardiness. Extensive experiments are tested to investigate how Seru Production reduces the total tardiness.
The heterogeneity in biofilms is a major challenge in biofilm therapies due to different susceptibility of bacteria and extracellular polymeric substances (EPS) to antibacterial agents. Here, we ...describe a therapeutic strategy that overcame biofilm heterogeneity, where antibacterial agent (NO) and EPS dispersant (reactive oxygen species (ROS)‐inducing Fe3+) were separately loaded in the yolk and shell compartment of a yolk–shell nanoplatform. Compared with traditional combinational chemotherapies which suffer from inconsistent pharmacokinetics profiles, this strategy drew on the pharmacokinetic complementarity of ROS and NO, where ROS with a short diffusion distance and a high redox potential corrupted the EPS, facilitating NO, which has a long diffusion distance and a broad antimicrobial spectrum, to penetrate the biofilm and eliminate the resident bacteria. Additionally, the construction of a three‐dimensional spherical biofilm model is novel and clinically relevant.
A therapeutic strategy to overcome biofilm heterogeneity is presented, in which antibacterial agent (NO) and extracellular polymeric substances (EPS) dispersant (reactive oxygen species (ROS)‐inducing Fe3+) are separately loaded in the yolk and shell compartment of a yolk–shell nanoplatform. The spatiotemporally ordered release manner and pharmacokinetic complementarity of ROS and NO improve the anti‐biofilm outcome synergistically.
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•A top-down composition design strategy was used in X-ray-stimulated afterglow.•The LaGaO3:Sb,Cr poses a super-long afterglow emission (>500 h) at ∼750 nm.•The optimization, and ...mechanism of persistent luminescence are highlighted.•In vivo bioimaging can be performed under low dose X-ray irradiation (0.37 Gy).
X-ray-stimulated near-infrared persistent luminescence nanoparticles (NIR-PLNPs) offer attractive capabilities for autofluorescence free deep-seated imaging and depth-independent treatment, but still suffer from adverse effects caused by high-dose X-ray irradiation (>5 Gy). From the viewpoint of two centers of NIR-PLNPs, i.e., X-ray photon absorption center and defects center, we here propose a top-down composition design strategy for the development of low dose X-ray-stimulated NIR-PLNPs with improved X-ray photon absorption efficiency and optimized persistent luminescence (PersL) performance. Successfully, hypersensitive X-ray-stimulated NIR-PLNPs LaGaO3:Sb3+,Cr3+ with a super-long PersL emission (>500 h) at ∼750 nm are prepared. The nature of high Z atomic constituents of the host LaGaO3 endows these NIR-PLNPs with strong X-ray absorption capacity. Simply by codoping with size-mismatched ions Sb3+, the concentration of oxygen vacancies in the host is rationally optimized, leading to the enhanced NIR PersL performance of Cr3+ ions. In vivo bioimaging demonstrates that the designed X-ray-stimulated NIR-PLNPs LaGaO3:Sb3+,Cr3+ can be readily reactivated under X-ray irradiation with even a lower dose to 0.37 Gy, showing the advantages of these nanoparticles on deep-seated imaging and treatment. More importantly, we anticipate that our proposed top-down composition design strategy can be applied to develop much low dose X-ray-stimulated NIR-PLNPs in the future.
The method based on the dispersive solid-phase extraction (DSPE) by novel molybdenum disulfide modified with carbon dot (MoS
2
/CD) composite combined with high-performance liquid chromatography ...(HPLC) was developed for the determination of three brominated flame retardants (BFRs), including tetrabromobisphenol A (TBBPA), tetrabromobisphenol A bisallylether (TBBPA-BAE), and tetrabromobisphenol A bis(2,3-dibromopropyl ether) (TBBPA-BDBPE). Owing to the stacked planar structure and large surface area of MoS
2
, a large number of CDs can be easily loaded on the surface of MoS
2
. Benefiting from good dispersing capability of MoS
2
, similar density with analytes, and hydrogen bonds between CDs and the target analytes, the CDs on the surface of MoS
2
as sorbent for the DSPE procedure exhibited good extraction performance. Under optimal conditions, application of the developed method to analyze BFRs from real water samples resulted in good recovery values ranging from 80 to 91% with relative standard deviation (RSD) values lower than 6.5%. Limits of detection (LODs) were in the range of 0.01–0.06 μg/L. The result above showed that the method has potential for the extraction and detection of trace-level BFRs from real water sample.
Graphical abstract
Owing to the stacked planar structure and large surface area of MoS
2
, a large number of CDs can be easily loaded on the surface of MoS
2
. Benefiting from good dispersing capability of MoS
2
, similar density with analytes, and hydrogen bonds between CDs and the target analytes, the prepared MoS
2
/CD composites as sorbent for the DSPE procedure exhibited good extraction performance. Accordingly, the extraction yield of BFRs was improved, which was favorable to its accurate determination in sample.
Proximal humerus fractures are common in clinical practice, and there are relatively a few studies on postoperative incision infections of such fractures. The purpose of this study was to explore the ...risk factors for surgical site infection (SSI) after internal fixation in patients with closed proximal humerus fractures. Patients with closed proximal humerus fractures who underwent surgery from January 2016 to January 2022 were retrospectively analysed. Cases with superficial or deep infections within 3 months after surgery were in the infection group and the remaining cases were in the non‐infection group. The types of pathogenic bacteria in the infection group were analysed. The potential risk factors for SSI in all patients were recorded: (1) patient‐related factors: gender, age, body mass index (BMI), smoking, comorbidities; (2) trauma‐related factors: mechanism of injury, Injury Severity Score, visual analogue scale, fracture type, soft tissue condition and combined dislocation; (3) laboratory‐related indexes: haemoglobin, albumin; (4) surgery‐related factors: time from injury to surgery, American Society of Anesthesiologists anaesthesia classification, surgical time, fixation mode, intraoperative blood loss, suture method, bone graft and postoperative drainage. The risk factors for the occurrence of SSI were analysed using univariate analysis and multivariate logistic regression. The incidence of SSI was 15.7%. The most common bacterium in the infection group was Staphylococcus aureus. High BMI (p = 0.033), smoking (p = 0.030), an increase in mean time from injury to definitive surgery (p = 0.013), and prolonged surgical time (p = 0.044) were independent risk factors for the development of SSI after closed proximal humeral fractures. In patients with closed proximal humerus fractures, weight loss, perioperative smoking cessation, avoidance of delayed surgery, and shorter surgical time may be beneficial in reducing the incidence of SSI.
Microwave-assisted and ultrasound-assisted extraction assays were used to isolate total flavonoids (TF) from
flowers. The effects of the solid-liquid ratio, ethanol concentration, microwave power, ...microwave extraction time, ultrasonic power and ultrasonic extraction time on the yield of TF were studied. A sequential combination of microwave- and ultrasound-assisted extraction (SC-MUAE) methods was developed, which was subsequently optimized by Box-Behnken design-response surface methodology (BBD-RSM). The interaction effects of the ethanol concentration (40-60%), microwave extraction time (5-7 min), ultrasonic extraction time (8-12 min) and ultrasonic power (210-430 W) on the yield of TF were investigated. The optimum operating parameters for the extraction of TF were determined to be as follows: ethanol concentration (48.15%), microwave extraction time (6.43 min), ultrasonic extraction time (10.09 min) and ultrasonic power (370.9 W). Under these conditions, the extraction yield of TF was 7.86 mg/g.
We performed a two-stage genome-wide association study of IgA nephropathy (IgAN) in Han Chinese, with 1,434 affected individuals (cases) and 4,270 controls in the discovery phase and follow-up of the ...top 61 SNPs in an additional 2,703 cases and 3,464 controls. We identified associations at 17p13 (rs3803800, P = 9.40 × 10(-11), OR = 1.21; rs4227, P = 4.31 × 10(-10), OR = 1.23) and 8p23 (rs2738048, P = 3.18 × 10(-14), OR = 0.79) that implicated the genes encoding tumor necrosis factor (TNFSF13) and α-defensin (DEFA) as susceptibility genes. In addition, we found multiple associations in the major histocompatibility complex (MHC) region (rs660895, P = 4.13 × 10(-20), OR = 1.34; rs1794275, P = 3.43 × 10(-13), OR = 1.30; rs2523946, P = 1.74 × 10(-11), OR = 1.21) and confirmed a previously reported association at 22q12 (rs12537, P = 1.17 × 10(-11), OR = 0.78). We also found that rs660895 was associated with clinical subtypes of IgAN (P = 0.003), proteinuria (P = 0.025) and IgA levels (P = 0.047). Our findings show that IgAN is associated with variants near genes involved in innate immunity and inflammation.
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