Konjac glucomannan/microcapsule of thymol edible coating reduces okra pericarp browning by regulating antioxidant activity and ROS synthesis.

Okra is susceptible to browning during storage. The effects of konjac glucomannan/microcapsule of thymol edible coating (TKL) on antioxidant activity and reactive oxygen (ROS) synthesis of okra during low-temperature storage were investigated. Thymol edible coating of thymol concentration 40 mg/mL (TKL40) had a regulatory effect on okra browning. After 14 days of storage, compared with the control group, the weight loss rate of TKL was reduced by 5.26 %, the hardness was increased by 24.14 %, and the L⁎ value was increased by 31 %. Moreover, TKL40 increased the scavenging capacity of okra for DPPH and ABTS free radicals, and activated catalase and superoxide dismutase activities by promoting the accumulation of total phenolics and flavonoids. TKL40 also reduced the cell membrane damage of okra during low-temperature storage by reducing the increase of malondialdehyde and H2O2 during okra storage. Meanwhile, it delayed the increase of relative conductivity and the production of O2.-, inhibited the activity of polyphenol oxidase in the late stage, so reduced the combination of polyphenol oxidase and phenolics to reduce the browning. Therefore, TKL40 reduces okra pericarp browning by regulating antioxidant activity and ROS synthesis.

The corrosion behavior of carbon steel under coexistence of carbon dioxide and SRB.

The corrosion behavior of carbon steel under the coexistence of carbon dioxide and SRB was studied by means of corrosion weight loss, SEM, EDS, in situ pH test, and other methods. The results showed that Chloride ions, temperature, pH, and oxygen coexist with iron bacteria will affect the corrosion under the coexistence of CO2 and SRB, and SRB tends to grow in a favorable environment for itself, and the corrosion rate of X52N at 42 days is slightly higher than that at 21 days. However, the pitting depth increased sharply from 21.20 µm in 21 days to 39.79 µm in 42 days. So that the corrosion can be divided into two stages. First, SRB catalyze the dissolution of FeCO3, leading to local uniform corrosion. Second, SRB directly obtain electrons from the metal surface, resulting in local pitting. In addition, the environment under the stable mineralized biofilm was found to be slightly alkaline.

Medium-chain triglycerides combined with DHA improve cognitive function by inhibiting neurocyte apoptosis of the brain in SAMP8 mice.

Medium-chain triglycerides (MCTs) and docosahexaenoic acid (DHA, Cn-3, 22:6) are essential in improving cognitive function and protecting neurocytes. This study explored the effects of the combined intervention of MCTs and DHA on inhibiting neurocyte apoptosis of the brain and improving cognitive function in senescence-accelerated mouse-prone 8 (SAMP8). Four-month-old male SAMP8 mice were randomly divided into four treatment groups (12 mice/group): DHA, MCT, DHA + MCT, and control groups, which intervened for seven months. Twelve age-matched male senescence-accelerated mouse resistant 1 (SAMR1) was used as the natural aging group. TUNEL assay and HE staining were used to assess neurocyte apoptosis and damage in the brain of mice. Moreover, the cognitive function was analyzed using the Morris water maze (MWM) and open field (OF) tests. The results showed that the cognitive function of 11-month-old SAMP8 mice decreased with age, and further pathological examination revealed the damaged neurocyte structure, karyopyknosis, cell atrophy, and even apoptosis. MCTs combined with DHA supplementation could increase octanoic acid (C8:0), decanoic acid (C10:0), and DHA levels in the serum, inhibit neurocyte apoptosis, improve neurocyte damage, moreover delay age-related cognitive decline after seven-month treatment. Furthermore, combining MCTs and DHA was significantly more beneficial than MCTs or DHA alone. In conclusion, MCTs combined with DHA could delay cognitive decline by inhibiting neurocyte apoptosis of the brain in SAMP8 mice.

Cognitive benefits of folic acid, docosahexaenoic acid and a combination of both nutrients in mild cognitive impairment; possible alterations though mitochondrial function and DNA damage.

INTRODUCTION: It is uncertain whether folic acid (FA) combined with docosahexaenoic acid (DHA) could improve cognitive performance. This study evaluated the effects of a 12-month FA and DHA supplementation, in combination or alone, on cognitive function, DNA oxidative damage, and mitochondrial function in participants with mild cognitive impairment (MCI). METHODS: This randomized, double-blind, placebo-controlled trial recruited MCI participants aged 60 years and older. Two hundred and eighty participants were randomly divided in equal proportion into four groups: FA+DHA (FA 800µg/d + DHA 800mg/d), FA (800µg/d), DHA (800mg/d), and placebo groups daily orally for 12 months. The primary outcome was cognitive function evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-RC). Cognitive tests and blood mechanism-related biomarkers were determined at baseline and 12 months. RESULTS: During the 12-month follow, scores of full intelligence quotient (FIQ) (ßDHA: 1.302, 95%CI: 0.615, 1.990, p < 0.001; ßFA: 1.992, 95%CI: 1.304, 2.679, p < 0.001; ßFA+DHA: 2.777, 95%CI: 2.090, 3.465, p < 0.001), verbal intelligence quotient, and some subtests of the WAIS-RC were significantly improved in FA+DHA and single intervention groups compared to the placebo group. Moreover, the FA and DHA intervention combination was superior to either intervention alone (p < 0.001). Meanwhile, FA, DHA and their combined use significantly decreased 8-OHdG level and increased mitochondrial DNA copy number compared to the placebo (p < 0.05). CONCLUSIONS: Supplementation of FA and DHA, alone or combined, for 12 months can improve cognitive function in MCI participants, possibly through mitigating DNA oxidative damage and enhancing mitochondrial function. Combined supplementation may provide more cognitive benefit than supplementation alone. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000034351. Registered 3 July 2020 - Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=53345.

[Applications of chromatography in glycomics].

Glycomics, an emerging "omics" technology that was developed after genomics and proteomics, is a discipline that studies the composition, structure, and functions of glycomes in cells, tissues, and organisms. Glycomics plays key roles in understanding the laws of major life activities, disease prevention and treatment, and drug quality control and development. At present, the structural analysis of glycans relies mainly on mass spectrometry. However, glycans have low abundance in biological samples. In addition, factors such as variable monosaccharide compositions, differences in glycosidic bond positions and modes, diverse branching structures, contribute to the complexity of the compositions and structures of glycans, posing great challenges to glycomics research. Liquid chromatography can effectively remove matrix interferences and enhance glycan separation to improve the mass spectrometric response of glycans. Thus, liquid chromatography and liquid chromatography coupled with mass spectrometry are important technical tools that have been actively applied to solve these problems; these technologies play indispensable roles in glycomics research. Different studies have highlighted similarities and differences in the applications of various types of liquid chromatography, which also reflects the versatility and flexibility of this technology. In this review, we first discuss the enrichment methods for glycans and their applications in glycomics research from the perspective of chromatographic separation mechanisms. We then compare the advantages and disadvantages of these methods. Some glycan-enrichment modes include affinity, hydrophilic interactions, size exclusion, and porous graphitized carbon adsorption. A number of newly developed materials exhibit excellent glycan-enrichment ability. We enumerate the separation mechanisms of reversed-phase high performance liquid chromatography (RP-HPLC), high performance anion-exchange chromatography (HPAEC), hydrophilic interaction chromatography (HILIC), and porous graphitic carbon (PGC) chromatography in the separation and analysis of glycans, and describe the applications of these methods in the separation of glycans, glycoconjugates, and glyco-derivatives. Among these methods, HILIC and PGC chromatography are the most widely used, whereas HPAEC and RP-HPLC are less commonly used. The HILIC and RP-HPLC modes are often used for the separation of derived glycans. The ionization efficiency and detectability of glycans are significantly improved after derivatization. However, the derivatization process is relatively cumbersome, and byproducts inevitably affect the accuracy and completeness of the detection results. HPAEC and PGC chromatography exhibit good separation effects on nonderivative glycans, but issues related to the detection integrity of low-abundance glycans owing to their poor detection effect continue to persist. Therefore, the appropriate analytical method for a specific sample or target analyte or mutual verification must be selected. Finally, we highlight the research progress in various chromatographic methods coupled with mass spectrometry for glycomics analysis. Significant progress has been made in glycomics research in recent years owing to advancements in the development of chromatographic separation techniques. However, several significant challenges remain. As the development of novel separation materials and methods continues, chromatographic techniques may be expected to play a critical role in future glycomics research.

Real-life effectiveness and safety of vedolizumab in moderate-to-severe ulcerative colitis: A single-center experience in Northern China.

Vedolizumab (VDZ), a monoclonal antibody to α4ß7 integrin, is available for patients with moderate-to-severe ulcerative colitis (UC). This study planned to assess the real-world effectiveness and safety of VDZ for UC patients in Northern China. We enrolled patients with moderate-to-severe UC who underwent VDZ induction therapy from March 2021 to November 2022 at the Affiliated Hospital of Qingdao University. The primary outcome was clinical remission at weeks 14 and 52 after the initial VDZ therapy. Overall adverse events and risk factors associated with loss of response (LOR) were also evaluated. Seventy-three UC patients receiving VDZ therapy were included in this study. The rates of clinical response, clinical remission, and steroid-free clinical remission were 69.9%, 39.7%, and 34.2% at week 14 and 90.5%, 66.7%, and 64.4% at week 52, respectively. The mucosal remission rates were 37.5% (18/48) at week 14 ±â€…8 and 27.3% (9/33) at week 52 ±â€…16, while only 2 and 3 patients achieved mucosal healing at weeks 14 ±â€…8 and 52 ±â€…16, respectively. Of the UC patients, 23.3% experienced adverse events associated with VDZ, most of which were mild and self-limiting. Until the last follow-up, 37 of 73 UC patients experienced LOR during the maintenance period. Patients with a higher ulcerative colitis endoscopic severity index (UCEIS), partial Mayo scores (PMS), or hemoglobin below 120 g/L at baseline were more likely to experience LOR after VDZ induction therapy. VDZ is an effective and safe agent for patients with moderate-to-severe UC in Northern China. A high baseline UCEIS, PMS, or hemoglobin < 120 g/L may be an independent risk factor for LOR during the maintenance period.

Macrophage membrane-reversibly camouflaged nanotherapeutics accelerate fracture healing by fostering MSCs recruitment and osteogenic differentiation.

The fracture healing outcome is largely dependent on the quantities as well as osteogenic differentiation capacities of mesenchymal stem cells (MSCs) at the lesion site. Herein, macrophage membrane (MM)-reversibly cloaked nanocomplexes (NCs) are engineered for the lesion-targeted and hierarchical co-delivery of short stromal derived factor-1α peptide (sSDF-1α) and Ckip-1 small interfering RNA (Ckip-1 siRNA, siCkip-1) to promote bone repair by concurrently fostering recruitment and osteogenic differentiation of endogenous MSCs. To construct the NCs, a membrane-penetrating α-helical polypeptide first assembles with siCkip-1, and the cationic NCs are sequentially coated with catalase and an outer shell of sSDF-1α-anchored MM. Due to MM-assisted inflammation homing, intravenously injected NCs could efficiently accumulate at the fractured femur, where catalase decomposes the local hydrogen peroxide to generate oxygen bubbles that drives the shedding of sSDF-1α-anchored MM in the extracellular compartment. The exposed, cationic inner core thus enables robust trans-membrane delivery into MSCs to induce Ckip-1 silencing. Consequently, sSDF-1α-guided MSCs recruitment cooperates with siCkip-1-mediated osteogenic differentiation to facilitate bone formation and accelerate bone fracture healing. This study provides an enlightened strategy for the hierarchical co-delivery of macromolecular drugs into different cellular compartments, and it also renders a promising modality for the management of fracture healing.

Comparative Analysis of Texture Characteristics, Sensory Properties, and Volatile Components in Four Types of Marinated Tofu.

In this study, three different brands of commercially available marinated tofu were analyzed and compared with homemade products to explore the effect of key flavor substances on their sensory quality, sensory properties, texture characteristics, and volatile components. The texture characteristics and flavor substances of the three brands of commercially available marinated tofu were significantly different from those of homemade products. A total of 64 volatile components were identified by headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS), mainly including 11 hydrocarbons, 11 alcohols, 10 ketones, 15 aldehydes, 4 esters, 1 acid, and 12 other volatile substances. Among these, nine key flavor compounds (ROAV > 1, VIP > 1) were identified using the relative odor activity value (ROAV) combined with a partial least squares discriminant analysis (PLS-DA) and variable importance in projection, including α-Pinene, ß-Myrcene, α-Phellandrene, 1-Penten-3-one, Butanal, 3-Methyl butanal, acetic acid ethyl ester, 1,8-Cineol, and 2-Pentyl furan. The correlation heatmap showed that sensory evaluation was positively correlated with hardness, gumminess, chewiness, and springiness while negatively correlated with 2-Pentyl furan, α-Pinene, resilience, α-Phellandrene, 1-Penten-3-one, acetic acid ethyl ester, and 1,8-Cineol. Overall, this study provides a theoretical reference for developing new instant marinated tofu snacks.

Alpha-Synuclein Interaction with UBL3 Is Upregulated by Microsomal Glutathione S-Transferase 3, Leading to Increased Extracellular Transport of the Alpha-Synuclein under Oxidative Stress.

Aberrant aggregation of misfolded alpha-synuclein (α-syn), a major pathological hallmark of related neurodegenerative diseases such as Parkinson's disease (PD), can translocate between cells. Ubiquitin-like 3 (UBL3) is a membrane-anchored ubiquitin-fold protein and post-translational modifier. UBL3 promotes protein sorting into small extracellular vesicles (sEVs) and thereby mediates intercellular communication. Our recent studies have shown that α-syn interacts with UBL3 and that this interaction is downregulated after silencing microsomal glutathione S-transferase 3 (MGST3). However, how MGST3 regulates the interaction of α-syn and UBL3 remains unclear. In the present study, we further explored this by overexpressing MGST3. In the split Gaussia luciferase complementation assay, we found that the interaction between α-syn and UBL3 was upregulated by MGST3. While Western blot and RT-qPCR analyses showed that silencing or overexpression of MGST3 did not significantly alter the expression of α-syn and UBL3, the immunocytochemical staining analysis indicated that MGST3 increased the co-localization of α-syn and UBL3. We suggested roles for the anti-oxidative stress function of MGST3 and found that the effect of MGST3 overexpression on the interaction between α-syn with UBL3 was significantly rescued under excess oxidative stress and promoted intracellular α-syn to extracellular transport. In conclusion, our results demonstrate that MGST3 upregulates the interaction between α-syn with UBL3 and promotes the interaction to translocate intracellular α-syn to the extracellular. Overall, our findings provide new insights and ideas for promoting the modulation of UBL3 as a therapeutic agent for the treatment of synucleinopathy-associated neurodegenerative diseases.

Establishment and validation of a nomogram containing cytokeratin fragment antigen 21-1 for the differential diagnosis of intrahepatic cholangiocarcinoma and hepatocellular carcinoma.

Background: Our study aimed to develop a nomogram incorporating cytokeratin fragment antigen 21-1 (CYFRA21-1) to assist in differentiating between patients with intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC). Methods: A total of 487 patients who were diagnosed with ICC and HCC at Qilu Hospital of Shandong University were included in this study. The patients were divided into a training cohort and a validation cohort based on whether the data collection was retrospective or prospective. Univariate and multivariate analyses were employed to select variables for the nomogram. The discrimination and calibration of the nomogram were evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Decision curve analysis (DCA) was used to assess the nomogram's net benefits at various threshold probabilities. Results: Six variables, including CYFRA21-1, were incorporated to establish the nomogram. Its satisfactory discriminative ability was indicated by the AUC (0.972 for the training cohort, 0.994 for the validation cohort), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) values. The Hosmer-Lemeshow test and the calibration plots demonstrated favorable consistency between the nomogram predictions and the actual observations. Moreover, DCA revealed the clinical utility and superior discriminative ability of the nomogram compared to the model without CYFRA21-1 and the model consisting of the logarithm of alpha-fetoprotein (Log AFP) and the logarithm of carbohydrate antigen 19-9 (Log CA19-9). Additionally, the AUC values suggested that the discriminative ability of Log CYFRA21-1 was greater than that of the other variables used as diagnostic biomarkers. Conclusions: This study developed and validated a nomogram including CYFRA21-1, which can aid clinicians in the differential diagnosis of ICC and HCC patients.

Two-pronged anti-cancer nanovaccines enpowered by exogenous/endogenous tumor-associated antigens.

Cancer vaccines based on single-source (exogenous or endogenous) tumor-associated antigens (TAAs) are often challenged by the insufficient T cell response and the immunosuppressive tumor microenvironment (TME). Herein, a dual TAAs-boosted nanovaccine based on cancer cell (4T1) membrane-cloaked, CO-immobilized Prussian blue nanoparticles (4T1-PB-CO NPs) is developed and coupled with anti-interleukin (IL)-10 therapy to maximize the efficacy of antitumor immunotherapy. 4T1 cell membrane not only endows NPs with tumor targeting ability, but also serves as exogenous TAAs to trigger CD4+ T cell response and M1-phenotype polarization of tumor-associated macrophages. Under near-infrared light irradiation, 4T1-PB-CO NPs release CO to induce immunogenic cell death (ICD) of tumor cells, thus generating endogenous TAAs to activate CD8+ T cell response. Meanwhile, ICD triggers release of damage-associated molecular patterns, which could promote DC maturation to amplify the antitumor T cell response. When combined with anti-IL-10 that reverses the immunosuppressive TME, 4T1-PB-CO NPs efficiently suppress the primary tumors and produce an abscopal effect to inhibit distant tumors in a breast tumor-bearing mouse model. Such a two-pronged cancer vaccine represents a promising paradigm for robust antitumor immunotherapy.

Spexin inhibits excessive autophagy-induced ferroptosis to alleviate doxorubicin-induced cardiotoxicity by upregulating Beclin 1.

BACKGROUND AND PURPOSE: Doxorubicin is widely used in the treatment of malignant tumours, but doxorubicin-induced cardiotoxicity severely limits its clinical application. Spexin is a neuropeptide that acts as a novel biomarker in cardiovascular disease. However, the effects of spexin on doxorubicin-induced cardiotoxicity is unclear. EXPERIMENTAL APPROACH: We established a model of doxorubicin-induced cardiotoxicity both in vivo and in vitro. Levels of cardiac damage in mice was assessed through cardiac function assessment, determination of serum cardiac troponin T and CKMB levels and histological examination. CCK8 and PI staining were used to assess the doxorubicin-induced toxicity in cultures of cardiomyocytes in vitro. Ferroptosis was assessed using FerroOrange staining, determination of MDA and 4-HNE content and ferroptosis-associated proteins SLC7A11 and GPX4. Mitochondrial membrane potential and lipid peroxidation levels were measured using TMRE and C11-BODIPY 581/591 probes, respectively. Myocardial autophagy was assessed by expression of P62 and Beclin1. KEY RESULTS: Spexin treatment improved heart function of mice with doxorubicin-induced cardiotoxicity, and attenuated doxorubicin-induced cardiotoxicity by decreasing iron accumulation, abnormal lipid metabolism and inhibiting ferroptosis. Interestingly, doxorubicin caused excessive autophagy in cardiomyocyte in culture, which could be alleviated by treatment with spexin. Knockdown of Beclin 1 eliminated the protective effects of spexin in mice with DIC. CONCLUSION AND IMPLICATIONS: Spexin ameliorated doxorubicin-induced cardiotoxicity by inhibiting excessive autophagy-induced ferroptosis, suggesting that spexin could be a drug candidate against doxorubicin-induced cardiotoxicity. Beclin 1 might be critical in mediating the protective effect of spexin against doxorubicin-induced cardiotoxicity.

Exploring the inverse relationship between serum total bilirubin and systemic immune-inflammation index: insights from NHANES data (2009-2018).

BACKGROUND: Bilirubin is known for its multifaceted attributes, including antioxidant, anti-inflammatory, immunomodulatory, and antiapoptotic properties. The systemic immune-inflammation index (SII) is a recent marker that reflects the balance between inflammation and immune response. Despite the wealth of information available on bilirubin's diverse functionalities, the potential correlation between the total bilirubin (TB) levels and SII has not been investigated so far. METHODS: Leveraging data from the National Health and Nutrition Examination Survey spanning 2009-2018, the TB levels were categorized using tertiles. Employing the chi-squared test with Rao and Scott's second-order correction and Spearman's rank correlation analysis, the association between TB and SII was examined. The potential nonlinearities between TB and SII were evaluated using restricted cubic spline (RCS) analysis. Weighted linear regression, adjusted for covariates, was used to explore the correlation between TB and SII, with further subgroup analyses. RESULTS: A total of 16,858 participants were included, and the findings revealed significant SII variations across TB tertiles (p < 0.001). The third tertile (Q3) exhibited the lowest SII level at 495.73 (295.00) 1000 cells/µL. Spearman rank correlation disclosed the negative association between TB and SII. RCS analysis exposed the lack of statistically significant variations in the nonlinear relationship (p > 0.05), thereby providing support for a linear relationship. Weighted linear regression analysis underscored the negative correlation between TB and SII (ß 95% CI - 3.9 [- 5.0 to - 2.9], p < 0.001). The increase in the TB levels is associated with a significant linear trend toward decreasing SII. After controlling for relative covariates, this negative correlation increased (p < 0.001). Subgroup analysis confirmed the significant negative TB-SII association. CONCLUSION: A notable negative correlation between TB and SII implies the potential protective effects of bilirubin in inflammation-related diseases.

A Mechanically Resilient Soft Hydrogel Improves Drug Delivery for Treating Post-Traumatic Osteoarthritis in Physically Active Joints.

Intra-articular delivery of disease-modifying osteoarthritis drugs (DMOADs) is likely to be most effective in early post-traumatic osteoarthritis (PTOA) when symptoms are minimal and patients are physically active. DMOAD delivery systems therefore must withstand repeated mechanical loading without affecting the drug release kinetics. Although soft materials are preferred for DMOAD delivery, mechanical loading can compromise their structural integrity and disrupt drug release. Here, we report a mechanically resilient soft hydrogel that rapidly self-heals under conditions resembling human running while maintaining sustained release of the cathepsin-K inhibitor L-006235 used as a proof-of-concept DMOAD. Notably, this hydrogel outperformed a previously reported hydrogel designed for intra-articular drug delivery, used as a control in our study, which neither recovered nor maintained drug release under mechanical loading. Upon injection into mouse knee joints, the hydrogel showed consistent release kinetics of the encapsulated agent in both treadmill-running and non-running mice. In a mouse model of aggressive PTOA exacerbated by treadmill running, L-006235 hydrogel markedly reduced cartilage degeneration. To our knowledge, this is the first hydrogel proven to withstand human running conditions and enable sustained DMOAD delivery in physically active joints, and the first study demonstrating reduced disease progression in a severe PTOA model under rigorous physical activity, highlighting the hydrogel's potential for PTOA treatment in active patients.

Characteristics and Controlling Factors of Methane Adsorption of the Longmaxi Shale in Northeastern Chongqing: Implications for Shale Gas Occurrence in Complex Structural Areas.

Accurately determining the adsorption capacity of Longmaxi shale in complex structural areas is crucial for evaluating the shale gas resources in northeastern Chongqing. However, studies on the pore characteristics and methane adsorption capacity of these Longmaxi shales are currently limited. In this paper, we collected core samples from the YDB-1 well in northeastern Chongqing and determined the pore structure and adsorption capacity of the Longmaxi shale using low-pressure gas adsorption and high-temperature, high-pressure methane adsorption experiments, respectively. The results indicate that the adsorption capacity of shale in complex structural areas is significantly positively correlated with the organic matter (OM) content, weakly positively correlated with the quartz content, and weakly negatively correlated with clay minerals. Meanwhile, gas-in-place content is simultaneously controlled by the pressure and temperature of the reservoir, and with increasing depth, the adsorbed gas rapidly increases to a maximum value (at 0.8 km) and then slowly decreases, whereas the free gas continuously increases. Compared with the shale in the stable structural areas, the Longmaxi shale in complex structural areas usually develops OM-hosted pores and intergranular pores of OM and minerals and contains more micropores due to tectonic compression, resulting in a relatively larger specific surface area and adsorption capacity. This is the reason shale in complex structural areas has high development potential. The final result can provide an important basis for the evaluation of the gas content and the optimization of dessert areas in the Lower Paleozoic shale gas in southern China.

Machine-learning-aided decision-making model for the discontinuation of continuous renal replacement therapy.

BACKGROUND: Continuous renal replacement therapy (CRRT) is a primary form of renal support for patients with acute kidney injury in an intensive care unit. Making an accurate decision of discontinuation is crucial for the prognosis of patients. Previous research has mostly focused on the univariate and multivariate analysis of factors in CRRT, without the capacity to capture the complexity of the decision-making process. The present study thus developed a dynamic, interpretable decision model for CRRT discontinuation. METHODS: The study adopted a cohort of 1234 adult patients admitted to an intensive care unit in the MIMIC-IV database. We used the extreme gradient boosting (XGBoost) machine learning algorithm to construct dynamic discontinuation decision models across four time points. Shapley additive explanation (SHAP) analysis was conducted to show the contribution of an individual feature to the model output. RESULTS: Of the 1234 included patients with CRRT, 596 (48.3%) successfully discontinued CRRT. The dynamic prediction by the XGBoost model produced an area under the curve of 0.848 and accuracy, sensitivity, and specificity of 0.782, 0.786, and 0.776, respectively. The XGBoost model was thus far superior to other test models. SHAP demonstrated that the features that contributed most to the model results were the sequential organ failure assessment score, serum lactate level, and 24-hour urine output. CONCLUSIONS: Dynamic decision models supported by machine learning are capable of dealing with complex factors in CRRT and effectively predicting the outcome of discontinuation.

Graphene/ chitosan tubes inoculated with dental pulp stem cells promotes repair of facial nerve injury.

Introduction: Facial nerve injury significantly impacts both the physical and psychological] wellbeing of patients. Despite advancements, there are still limitations associated with autografts transplantation. Consequently, there is an urgent need for effective artificial grafts to address these limitations and repair injuries. Recent years have witnessed the recognition of the beneficial effects of chitosan (CS) and graphene in the realm of nerve repair. Dental pulp stem cells (DPSCs) hold great promise due to their high proliferative and multi-directional differentiation capabilities. Methods: In this study, Graphene/CS (G/CST) composite tubes were synthesized and their physical, chemical and biological properties were evaluated, then DPSCs were employed as seed cells and G/CST as a scaffold to investigate their combined effect on promoting facial nerve injury repair. Results and Disscussion: The experimental results indicate that G/CST possesses favorable physical and chemical properties, along with good cyto-compatibility. making it suitable for repairing facial nerve transection injuries. Furthermore, the synergistic application of G/CST and DPSCs significantly enhanced the repair process for a 10 mm facial nerve defect in rabbits, highlighting the efficacy of graphene as a reinforcement material and DPSCs as a functional material in facial nerve injury repair. This approach offers an effective treatment strategy and introduces a novel concept for clinically managing facial nerve injuries.

Pygo-F773W Mutation Reveals Novel Functions beyond Wnt Signaling in Drosophila.

Pygopus (Pygo) has been identified as a specific nuclear co-activator of the canonical Wingless (Wg)/Wnt signaling pathway in Drosophila melanogaster. Pygo proteins consist of two conserved domains: an N-terminal homologous domain (NHD) and a C-terminal plant homologous domain (PHD). The PHD's ability to bind to di- and trimethylated lysine 4 of histone H3 (H3K4me2/3) appears to be independent of Wnt signaling. There is ongoing debate regarding the significance of Pygo's histone-binding capacity. Drosophila Pygo orthologs have a tryptophan (W) > phenylalanine (F) substitution in their histone pocket-divider compared to vertebrates, leading to reduced histone affinity. In this research, we utilized CRISPR/Cas9 technology to introduce the Pygo-F773W point mutation in Drosophila, successfully establishing a viable homozygous Pygo mutant line for the first time. Adult mutant flies displayed noticeable abnormalities in reproduction, locomotion, heart function, and lifespan. RNA-seq and cluster analysis indicated that the mutation primarily affected pathways related to immunity, metabolism, and posttranslational modification in adult flies rather than the Wnt signaling pathway. Additionally, a reduction in H3K9 acetylation levels during the embryonic stage was observed in the mutant strains. These findings support the notion that Pygo plays a wider role in chromatin remodeling, with its involvement in Wnt signaling representing only a specific aspect of its chromatin-related functions.

Bearing Rigidity-Based Flocking Control of AUVs via Semi-Supervised Incremental Broad Learning.

Flocking control of autonomous underwater vehicles (AUVs) has been regarded as the basis of many sophisticated marine coordination missions. However, there is still a research gap on the flocking of AUVs in weak communication and complex marine environment. This article attempts to fill up the above research gap from graph theory and intelligent learning perspectives. We first employ the bearing rigidity graph to describe the topology relationships of AUVs, through which an iterative gradient decent-based localization estimator is provided to obtain the position information. In order to improve the localization accuracy and energy efficiency, a min-weighted bearing rigidity graph generation strategy is developed. Along with this, we adopt the semi-supervised broad learning system (BLS) to design the model-free flocking controllers for AUVs in obstacle environment. The innovations of this article are summarized as follows: 1) the min-weighted bearing rigidity-based localization strategy can balance the localization accuracy and communication consumption as compared to the neighboring rule-based solutions and 2) the semi-supervised broad learning-based flocking controller can decrease the training time and solve the label limit over the supervised learning-based controllers. Finally, simulation and experimental studies are provided to verify the effectiveness.

Social support, psychological capital, multidimensional job burnout, and turnover intention of primary medical staff: a path analysis drawing on conservation of resources theory.

BACKGROUND: Job burnout is a prevalent and emerging challenge in the primary medical system, causing mass turnover, especially of primary medical staff. Little attention has been paid to the different dimensions of job burnout (emotional exhaustion, personality disintegration, and reduced sense of achievement), which may hinder efforts to tackle high turnover intention among primary medical staff. From the perspective of conservation of resources theory, social support and psychological capital are basic resources with potential to diminish job burnout and thus lower turnover intention. However, there is insufficient research evidence on the relationships between social support, psychological capital, and the three dimensions of job burnout within the primary medical system. OBJECTIVES: Focusing on primary medical staff, this study conducts a path analysis to examine the correlations between two types of resources (social support and psychological capital) and the three dimensions of job burnout, and to test the impact of the latter on turnover intention. Based on the results, effective management strategies to improve the work stability of primary medical staff are proposed. METHODS: Multi-stage cluster random sampling was used to select participants in Anhui Province, China. Data were collected using a self-administered questionnaire containing measures of the main variables and demographic questions. In total, 1132 valid questionnaires were returned by primary medical staff. Structural equation modeling was used for path analysis of the data. RESULTS: Social support was negatively associated with emotional exhaustion (ß = - 0.088, P = 0.020), personality disintegration (ß = - 0.235, P < 0.001), and reduced sense of achievement (ß = - 0.075, P = 0.040). Moreover, psychological capital was negatively associated with emotional exhaustion (ß = - 0.079, P = 0.030), personality disintegration (ß = - 0.156, P < 0.001), and reduced sense of achievement (ß = - 0.432, P < 0.001). All three dimensions of job burnout positively affected turnover intention (emotional exhaustion: ß = 0.246, P < 0.001; personality disintegration: ß = 0.076, P = 0.040; reduced sense of achievement: ß = 0.119, P = 0.001). CONCLUSIONS: The results highlight the importance of social support and psychological capital for diminishing the three dimensions of job burnout for primary medical staff and, in turn, lowering their turnover intention. Accordingly, to alleviate job burnout and improve staff retention, material and psychological supports from leaders, colleagues, family, relatives, and friends are essential, as are measures to improve the psychological energy of primary medical staff.