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The present study sought to investigate the amelioration effects of enzymatically synthesized docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) on the high-fat diet (HFD)-induced kidney injury in mice. After 6 weeks of DHA-PS intervention, the mice's body weight in the 20 and 40 mg/kg DHA-PS groups decreased by 7.09% and 9.71%, respectively, compared to the HFD group. Especially, compared to the HFD group, 40 mg/kg DHA-PS treatment effectively reduced the levels of serum urea nitrogen by 68.48%, creatinine by 38.98%, kidney lipid accumulation (total cholesterol, triglycerides, and nonesterified fatty acids levels by 26.19%, 51.00%, and 26.11%), kidney or serum proinflammatory cytokines and enhanced the levels of kidney or serum oxidative stress parameters, except for malondialdehyde (MDA). Moreover, 40 mg/kg DHA-PS treatment decreased the expression levels of toll-like receptor 4 (TLR4) by 18.63%, IKKα by 31.81%, and p-p65 by 40.73% in the nuclear factor kappa-B pathway, thereby upregulating the expression levels of p-AMPKα by 64.93%, HSL by 99.60%, ATGL by 344.50%, PPARα by 162.02%, CPT1 by 167.95%, p-ACC1 by 144.92%, and p-SREBP1 by 1172.95%, and downregulating the expression levels of SREBP1 by 38.80%, ACC1 by 18.10%, and FAS by 82.28% in the AMPK pathway. Furthermore, our results also suggested that improving serum or kidney parameters and regulating intestinal microbial could affect each other after DHA-PS treatment. These results elucidated that DHA-PS could be a potential dietary supplement to alleviate HFD-induced kidney injury. PRACTICAL APPLICATION: Our results elucidated that DHA-PS could be a potential dietary supplement to alleviate HFD-induced kidney injury.

Background Cuproptosis is the most recently discovered form of regulated cell death (RCD) induced by intracellular copper. Growing evidence has indicated that cuproptosis plays a considerable role in tumorigenesis among various cancers. However, the role of cuproptosis in the development of colon cancer (CC) and its prognostic value remains to be investigated. Methods Five independent cohorts with CC were included in this study. Comprehensive bioinformatics analyses were used to explore the expression, molecular function, and prognostic value of the pivotal regulator of cuproptosis, ferredoxin 1 (FDX1). Correlation analyses and least absolute shrinkage and selection operation (LASSO) regression analyses were utilized to screen the optimal combination of cuproptosis-related genes for constructing a Cox proportional hazards model, and the cuproptosis-related risk score (CRRS) was calculated to stratify CC patients in prognosis. The immunology, tumor stemness index, and drug sensitivity of the CRRS-based subgroups were also investigated. Moreover, the expression and biological functions of FDX1 were validated in vitro. Results Results showed that FDX1 was significantly downregulated in CC and its lower expression indicated poorer outcomes. Seven cuproptosis-associated genes were selected to construct the prognostic model. CRRS displayed good performance in predicting prognosis compared with clinical features. Moreover, CRRS could significantly enhance the prognostic prediction precision of the classic tumor, nodes, and metastases (TNM) staging system. The high-CRRS group showed an obvious immunosuppressive microenvironment and a lower stemness index compared with the low-CRRS group. The difference in FDX1 expression between CC and normal tissues was verified in vitro. Overexpression of FDX1 promoted cell death and inhibited cell proliferation and migration. Conclusions Our results suggest that CRRS can function as a good prognostic indicator for CC patients and may help guide treatment management. Our findings provide new insights into cuproptosis-targeted therapies for CC patients.

Objective. The main objective is to compare the clinical efficacy of the early use of dynamic orthosis in patients with a finger extensor digitorum rupture. Methods. A total of 50 patients with hand and foot trauma who received surgical treatment in our hospital from March 2017 to February 2021 were selected, and two patients were excluded from the study. The patients were randomly divided into two groups. The control group (group A) was treated with plaster fixation and routine rehabilitation, and the study group (group B) underwent dynamic low-temperature thermoplastic plate fixation and routine rehabilitation. Total active motion (TAM) and total passive motion (TPM) of the injured finger before treatment, one month after treatment, two months after treatment, and after corrective treatment were compared. Results. After treatment following a finger extensor digitorum rupture, the TAM and TPM of the injured fingers increased significantly in both groups. The TAM and TPM in group B were significantly better than those in group A after one and two months of treatment ( P < 0.05 ). After two months of treatment, the rates of improvement in TAM and TPM in group B were significantly higher than those in group A. Conclusion. The early use of dynamic orthosis can significantly improve the motor function and motion amplitude of the injured finger, increase the elasticity and extension of the finger extensor digitorum, and promote the recovery of muscle strength. It is an effective corrective method for tendon contracture after finger extensor digitorum rupture and has great value in clinical application.

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Cranial nerve injury by a laryngeal mask airway is rare but a serious complication. The nerve injuries must be prevented during the intubation using a laryngeal mask airway. We report a female patient who complained of tongue numbness, slurred speech, and slight difficulty in swallowing solid food after a hand surgery. She was then diagnosed with unilateral lingual nerve and hypoglossal nerve injuries. Extreme head rotation, relatively small oral cavity, and wide rigid composition at the lower part of the novel laryngeal mask probably resulted in cranial nerve injury.

The current study aimed to investigate the potential ameliorative effects of pyrroloquinoline quinone (PQQ) on cyclophosphamide (CTX)-induced liver injury in mice. The liver injury model was established by injecting mice with CTX (80 mg/kg/day). Liver function indices, antioxidant enzyme activities, and inflammatory cytokines were evaluated. In addition, protein expression levels of the nuclear factor E2-related factor 2 (Nrf2) and nuclear factor kappa-B (NF-κB) pathways in the liver tissues were determined using western blot. The results indicated that PQQ decreased the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the malondialdehyde (MDA), interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) levels in the liver tissues. Moreover, PQQ enhanced the activities of oxidative stress markers to alleviate CTX induced oxidative stress. Furthermore, the expression levels of heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H quinone oxidoreductase 1 (NQO1) were significantly increased, and the expression levels of NF-κB p50, NF-κB p65, and inhibitor of NF-κB kinase alpha (IKKα) were significantly decreased after PQQ administration, suggesting that PQQ alleviated CTX-induced liver injury via activating the Nrf2-mediated antioxidant response pathway, and inhibiting the NF-κB-mediated inflammation pathway. Therefore, PQQ can be potentially used as a dietary supplement or functional foods for alleviating the CTX-induced liver injury.

Argonaute 2 (Ago2) is an essential component of the RNA-induced silencing complex (RISC) and it participates in diverse physiological processes, while dysregulation of Ago2 activity is closely linked to a variety of human diseases including cancers. The reported Ago2 assays often suffer from laborious procedures, complicated reaction schemes, and unsatisfactory sensitivity. Herein, we develop a new gold nanoparticle (AuNP)-based single-molecule biosensor for simple and sensitive detection of Ago2 activity. The Ago2-responsive AuNP nanoprobe is constructed through the self-assembly of multiple Cy5-labeled signal probes onto the AuNP, in which the Cy5 fluorescence is efficiently quenched by the AuNP. Target Ago2 can bind with guide RNA to form an active RISC, inducing the cyclic cleavage of the signal probes and the release of Cy5 moieties from the AuNP nanoprobe. The released Cy5 molecules can be simply quantified by single-molecule counting. This single-molecule biosensor enables detection of Ago2 activity with the involvement of only a single AuNP nanoprobe, eliminating the use of any extra antibodies and protein enzymes. This single-molecule biosensor achieves good specificity and high sensitivity with a detection limit of 9.1 pM, and it can be exploited for the screening of Ago2 inhibitors, Ago2 kinetic analysis, and the imaging of intracellular Ago2 activity in live cells, holding great promise in Ago2-related biomedical research and clinical diagnosis.

DHA-enriched phosphatidylcholine from Clupea harengus roes could likely be used as a functional food supplement for the prevention of high-fat diet-induced non-alcoholic fatty liver disease via the gut–liver axis.

Protein kinases play important roles in regulating various cellular processes and may function as potential diagnostic and therapeutic targets for various diseases including cancers. Herein, we construct a phos-tag-directed self-assembled fluorescent magnetobiosensor to simultaneously detect multiple protein kinases with good selectivity and high sensitivity. In the presence of protein kinases (

Protein kinase can catalyze the phosphorylation of peptides/proteins, and it is closely associated with various human diseases such as cancer, immune deficiencies, and Alzheimer's disease. Sensitive monitoring of protein kinase activity is significant for biochemical research and drug discovery. Herein, we develop a phos-tag-based fluorescent biosensor for sensitive detection of cAMP-dependent protein kinase (PKA) activity in cancer cells. We design a peptide-DNA conjugate and a signal probe for PKA activity assay, and employ a biotinylated phos-tag (a selective phosphate-binding agent) to recognize and capture the phosphorylated peptide-DNA substrate. The peptide-DNA conjugates as the catalytic substrates can translate the peptide signal to a nucleotide signal for the initiation of the RNase HII-driven cycling signal amplification. The magnetic nanobeads (MBs) as the carriers can separate and enrich the phosphorylated peptide in complex matrices. Meanwhile, the combination of MBs with the phos-tag-mediated phosphate group recognition can effectively eliminate the interference from the complex matrix, and the introduction of single-molecule detection endows this assay with high sensitivity. This biosensor can achieve a detection limit of 1.98 × 10

In order to study the influence of geometric nonlinearity and material parameters on the free vibration behavior of the cylindrical skeleton supported prestressed fabric composite membrane. In this paper, based on von Karman's large deflection theory and D’Alembert's principle, the governing equations of nonlinear viscous damped prestressed free vibration of frame supported anisotropic membrane structures were established. By using Galerkin and KBM perturbation method, the analytical expressions of frequency function, displacement function and mode shape of nonlinear free vibration were obtained. In order to verify the effectiveness and effective range of the method, the fourth order Runge-Kutta method was used for numerical calculation. The calculation examples of membrane material parameters were given. The calculation and analysis of different membrane prestress, different length width ratio, different rise span ratio and different material parameters (elastic modulus ratio, viscous damping and material density) were carried out. The results were compared with the numerical results obtained by Runge-Kutta method to verify the accuracy of the method. The research results of this paper provide a theoretical reference for the selection of membrane materials, the subsequent calculation of wind-induced stability of steel skeleton membrane structure and the design of wind-driven rain resistance.

Background Abnormal alternative splicing is frequently associated with carcinogenesis. In B-cell acute lymphoblastic leukemia (B-ALL), double homeobox 4 fused with immunoglobulin heavy chain (DUX4/IGH) can lead to the aberrant production of E-26 transformation-specific family related gene abnormal transcript (ERGalt ) and other splicing variants. However, the molecular mechanism underpinning this process remains elusive. Here, we aimed to know how DUX4/IGH triggers abnormal splicing in leukemia. Methods The differential intron retention analysis was conducted to identify novel DUX4/IGH-driven splicing in B-ALL patients. X-ray crystallography, small angle X-ray scattering (SAXS), and analytical ultracentrifugation were used to investigate how DUX4/IGH recognize double DUX4 responsive element (DRE)-DRE sites. The ERGalt biogenesis and B-cell differentiation assays were performed to characterize the DUX4/IGH crosslinking activity. To check whether recombination-activating gene 1/2 (RAG1/2) was required for DUX4/IGH-driven splicing, the proximity ligation assay, co-immunoprecipitation, mammalian two hybrid characterizations, in vitro RAG1/2 cleavage, and shRNA knock-down assays were performed. Results We reported previously unrecognized intron retention events in C-type lectin domain family 12, member A abnormal transcript (CLEC12Aalt ) and chromosome 6 open reading frame 89 abnormal transcript (C6orf89alt ), where also harbored repetitive DRE-DRE sites. Supportively, X-ray crystallography and SAXS characterization revealed that DUX4 homeobox domain (HD)1-HD2 might dimerize into a dumbbell-shape trans configuration to crosslink two adjacent DRE sites. Impaired DUX4/IGH-mediated crosslinking abolishes ERGalt , CLEC12Aalt , and C6orf89alt biogenesis, resulting in marked alleviation of its inhibitory effect on B-cell differentiation. Furthermore, we also observed a rare RAG1/2-mediated recombination signal sequence-like DNA edition in DUX4/IGH target genes. Supportively, shRNA knock-down of RAG1/2 in leukemic Reh cells consistently impaired the biogenesis of ERGalt , CLEC12Aalt , and C6orf89alt . Conclusions All these results suggest that DUX4/IGH-driven DNA crosslinking is required for RAG1/2 recruitment onto the double tandem DRE-DRE sites, catalyzing V(D)J-like recombination and oncogenic splicing in acute lymphoblastic leukemia.

The 7th edition of the International Union against Cancer/American Joint Committee on Cancer (UICC/AJCC) manual defines new classification rules for nasopharyngeal carcinoma (NPC). The study was conducted to assess its effectiveness in predicting the prognosis of patients in Hunan Province, China. Between January 2001 and December 2004, 84 primary NPC patients with detailed clinical information were collected. We retrospectively analyzed the follow-up data of these patients in Sep 2007, July 2009, July 2010, Dec 2013, and Nov 2020. The 7th edition of the AJCC system creates subgroups (stages I to IV) that are assigned to 10 (11.9%), 31 (36.9%), 27 (32.2%), and 16 (19.0%) patients, respectively. The 7th edition of the AJCC system showed highly significant differences in gender for DFS. In the 7th version of the AJCC the overall stages, T classifications, and N classification showed a significant correlation with OS and disease-free survival (DFS). Multivariate analysis showed that T classification and N classification were independently significant prognostic factors for DFS and OS with 6-years. In conclusion, the 7th edition of the AJCC system for NPC is prognostically useful for patients from Hunan Province.