Pyroptosis-mediator GSDMD promotes Parkinson's disease pathology via microglial activation and dopaminergic neuronal death.

GSDMD-mediated pyroptosis occurs in the nigrostriatal pathway in Parkinson's disease animals, yet the role of GSDMD in neuroinflammation and death of dopaminergic neurons in Parkinson's disease remains elusive. Here, our in vivo and in vitro studies demonstrated that GSDMD, as a pyroptosis executor, contributed to glial reaction and death of dopaminergic neurons across different Parkinson's disease models. The ablation of the Gsdmd attenuated Parkinson's disease damage by reducing dopaminergic neuronal death, microglial activation, and detrimental transformation. Disulfiram, an inhibitor blocking GSDMD pore formation, efficiently curtailed pyroptosis, thereby lessening the pathology of Parkinson's disease. Additionally, a modification in GSDMD was identified in the blood of Parkinson's disease patients in contrast to healthy subjects. Therefore, the detected alteration in GSDMD within the blood of Parkinson's disease patients and the protective impact of disulfiram could be promising for the diagnostic and therapeutic approaches against Parkinson's disease.

A Diary Study of Daily Negative Aging Stereotypes and Goal Pursuit in Older Adults.

OBJECTIVES: This study aimed to investigate the association between negative aging stereotypes and goal pursuit in daily life among older adults. We also explored the roles of stereotype threat and stereotype challenge reactions in mediating this association. Additionally, this study investigated whether variations in these associations exist among older adults based on their self-integrity levels. METHODS: Participants were 100 older adults who completed daily measures assessing negative aging stereotype experiences, threat and challenge reactions, goal pursuit activities, and self-integrity over a week. RESULTS: More daily experiences of negative aging stereotypes were associated with greater avoidance of responsibilities in goal pursuit and less progress toward goals. Increased threat reactions and decreased challenge reactions were mediators of the association between stereotype experiences and avoidance of responsibilities, as well as that between stereotype experiences and progress toward goals, respectively. Moreover, the associations between threat reactions and avoidance of responsibilities as well as between stereotype experiences and challenge reactions were more pronounced in older adults with lower self-integrity levels. DISCUSSION: This study is pioneering in demonstrating the real-life interplay between aging stereotypes and goal pursuit among older adults. Its findings not only expand upon the literature concerning aging stereotypes, but also offer theoretical insights for the development of interventions aimed at goal pursuit. These insights have significant implications for fostering healthy aging.

Predictive value of delta radiomics in xerostomia after chemoradiotherapy in patients with stage III-IV nasopharyngeal carcinoma.

BACKGROUND: Xerostomia is one of the most common side effects in nasopharyngeal carcinoma (NPC) patients after chemoradiotherapy. To establish a Delta radiomics model for predicting xerostomia secondary to chemoradiotherapy for NPC based on magnetic resonance T1-weighted imaging (T1WI) sequence and evaluate its diagnostic efficacy. METHODS: Clinical data and Magnetic resonance imaging (MRI) data before treatment and after induction chemotherapy (IC) of 255 NPC patients with stage III-IV were collected retrospectively. Within one week after CCRT, the patients were divided into mild (92 cases) and severe (163 cases) according to the grade of xerostomia. Parotid glands in T1WI sequence images before and after IC were delineated as regions of interest for radiomics feature extraction, and Delta radiomics feature values were calculated. Univariate logistic analysis, correlation, and Gradient Boosting Decision Tree (GBDT) methods were applied to reduce the dimension, select the best radiomics features, and establish pretreatment, post-IC, and Delta radiomics xerostomia grading predictive models. The receiver operating characteristic (ROC) curve and decision curve were drawn to evaluate the predictive efficacy of different models. RESULTS: Finally, 15, 10, and 12 optimal features were selected from pretreatment, post-IC, and Delta radiomics features, respectively, and a xerostomia prediction model was constructed with AUC values of 0.738, 0.751, and 0.843 in the training set, respectively. Only age was statistically significant in the clinical data of both groups (P < 0.05). CONCLUSION: Delta radiomics can predict the degree of xerostomia after chemoradiotherapy for NPC patients and it has certain guiding significance for clinical early intervention measures.

Early prediction of long-term survival of patients with nasopharyngeal carcinoma by multi-parameter MRI radiomics.

Purpose: The objective is to create a comprehensive model that integrates clinical, semantic, and radiomics features to forecast the 5-year progression-free survival (PFS) of individuals diagnosed with non-distant metastatic Nasopharyngeal Carcinoma (NPC). Methods: In a retrospective analysis, we included clinical and MRI data from 313 patients diagnosed with primary NPC. Patient classification into progressive and non-progressive categories relied on the occurrence of recurrence or distant metastasis within a 5-year timeframe. Initial screening comprised clinical features and statistically significant image semantic features. Subsequently, MRI radiomics features were extracted from all patients, and optimal features were selected to formulate the Rad-Score.Combining Rad-Score, image semantic features, and clinical features to establish a combined model Evaluation of predictive efficacy was conducted using ROC curves and nomogram specific to NPC progression. Lastly, employing the optimal ROC cutoff value from the combined model, patients were dichotomized into high-risk and low-risk groups, facilitating a comparison of 10-year overall survival (OS) between the groups. Results: The combined model showcased superior predictive performance for NPC progression, reflected by AUC values of 0.84, an accuracy rate of 81.60%, sensitivity at 0.77, and specificity at 0.81 within the training group. In the test set, the AUC value reached 0.81, with an accuracy of 74.6%, sensitivity at 0.82, and specificity at 0.66. Conclusion: The amalgamation of Rad-Score, clinical, and imaging semantic features from multi-parameter MRI exhibited significant promise in prognosticating 5-year PFS for non-distant metastatic NPC patients. The combined model provided quantifiable data for informed and personalized diagnosis and treatment planning.

A new strategy to strongly release sweet-enhancing volatiles from goji pomace using trivalent iron salts.

Efforts to fully utilize pomace volatiles have been obstructed by the lack of high-performance technologies to release free and bound volatiles. This study first established that ferric chloride (FeCl3) could strongly release the sweet-enhancing volatiles (SVs) from goji pomace, thus increasing the main aroma compounds [MACs; odor activity value (OAV) > 1] from 9 to 27. The underlying mechanism included the special hydrolysis to glycosides by ferric ions acting as Brønsted and Lewis acids, and the oxidation of ß-carotene and ß-ionone by electrophilic ferrite. The sweet fragrance could be reconstituted and simulated by the 27 MACs. Subsequent extraction and concentration increased MACs on average by 2.28-fold, and the extracted essence could be used as a green and safe sweet-enhancing sugar substitute for specific consumers. These study findings laid a foundation for understanding the relationship between metal salts and flavor chemistry, further providing an opportunity for the full utilization of resources.

Metal coordinating-induced self-assembly of cyclic lipopeptides into high-performance antimicrobial supramolecules.

This study designed a green hydrothermally-chelating approach to generate robust antimicrobial complexes via metal-coordinated supramolecular self-assembly of cyclic lipopeptides (CLs). The metal ion (Ca2+ and Zn2+)-coordinated CL (Ca/CL or Zn/CL complex; 1 mg/mL) demonstrated potent antibacterial activity against fungi (A. niger) and bacteria (E. coli and S. aureus) respectively, and in particular, completely suppressed the microbial resistance. Further physicochemical and spectal analysis showed that this coordination approach led to CL with enhanced hydrophobic and intermolecular electrostatic interactions, forming ß-sheet-rich secondary structures allowing the complexes easily contact with and destroy the membrane of microorganisms. Practical application experiments validated that the Ca/CL and Zn/CL complexes strongly avoided table grape and fresh tomato from the contamination of pathogen. The findings of this study laid foundation for the utilization of metal ions to improve the biological activity of natural antimicrobial peptides.

Alteration of brain network centrality in CTN patients after a single triggering pain.

Objective: The central nervous system may also be involved in the pathogenesis of classical trigeminal neuralgia (CTN). The present study aimed to explore the characteristics of static degree centrality (sDC) and dynamic degree centrality (dDC) at multiple time points after a single triggering pain in CTN patients. Materials and methods: A total of 43 CTN patients underwent resting-state function magnetic resonance imaging (rs-fMRI) before triggering pain (baseline), within 5 s after triggering pain (triggering-5 s), and 30 min after triggering pain (triggering-30 min). Voxel-based degree centrality (DC) was used to assess the alteration of functional connection at different time points. Results: The sDC values of the right caudate nucleus, fusiform gyrus, middle temporal gyrus, middle frontal gyrus, and orbital part were decreased in triggering-5 s and increased in triggering-30 min. The sDC value of the bilateral superior frontal gyrus were increased in triggering-5 s and decreased in triggering-30 min. The dDC value of the right lingual gyrus was gradually increased in triggering-5 s and triggering-30 min. Conclusion: Both the sDC and dDC values were changed after triggering pain, and the brain regions were different between the two parameters, which supplemented each other. The brain regions which the sDC and dDC values were changing reflect the global brain function of CTN patients, and provides a basis for further exploration of the central mechanism of CTN.

Effects of traditional and advanced drying techniques on the physicochemical properties of Lycium barbarum L. polysaccharides and the formation of Maillard reaction products in its dried berries.

This study explored the effect of three different industrial drying methods on the physicochemical, nutritional, and safety profile of goji berries. The hot-air (HD) and microwave drying (MD) methods yielded berries with relatively high polysaccharide content, while vacuum freeze-drying (FD) yielded dried berries with better sensory qualities but relatively less polysaccharide content. The polysaccharides obtained from the HD and MD berries had lower molecular weight, high antioxidant activity and high degrees of Maillard reaction. Further investigations revealed that all three methods, in particular HD and MD, generated high levels of intermediate Maillard reaction products (55.8-86.3 mg/kg) and advanced glycation end-products (fluorescent intensity of 26784-51712), based on significant reduction of reducing sugar and amino acids in the HD and MD berries (p < 0.05). These findings highlight the need to scrutinize the effectiveness of traditional and emerging drying technologies used to produce safe fruits.

Comparison of chemical characterization and oxidative stability of Lycium barbarum seed oils: A comprehensive study based on processing methods.

Five different processing methods (cold pressing, hot pressing, solvent extraction, ultrasound-assisted solvent extraction, and supercritical fluid extraction) were evaluated to extract oils from Lycium barbarum (L. barbarum) seeds based on the lipid composition, minor bioactive components, and oxidative stability of oils. A large proportion of unsaturated fatty acids was detected in the L. barbarum seed oil, especially linoleic acid (65.24-66.26%). Minor bioactive components were abundant in L. barbarum seed oils, including tocopherols (292.65-488.49 mg/kg), phytosterols (9606.31-166,684.77 mg/kg), polyphenols (35.65-113.87 mg/kg), and carotenoid (4.17-46.16 mg/100 g). Specifically, the phytosterol content was higher than that of other common oils. Comparing the different processing techniques, ultrasound-assisted solvent extraction provided the highest extraction yield and recovery. The quantities of tocopherols, phenols, and phytosterols in hot-pressed oil were higher than those in oils extracted from other methods, and thus it had the best oxidative stability. L. barbarum seed oils extracted by different techniques showed various characteristics and could be distinguished through principal component analysis and hierarchical cluster analysis. PRACTICAL APPLICATION: L. barbarum seed oil is a potentially underutilized oil resource with abundant essential fatty acid and phytosterol, which owns great value to apply in the nutritional, cosmetic, and medicinal fields. Hot pressing is an efficient method to produce L. barbarum seed oil for health care with high nutritional value and good quality, which can also be easily implemented on an industrial scale.

Prediction of Response to Induction Chemotherapy Plus Concurrent Chemoradiotherapy for Nasopharyngeal Carcinoma Based on MRI Radiomics and Delta Radiomics: A Two-Center Retrospective Study.

Objective: We aimed to establish an MRI radiomics model and a Delta radiomics model to predict tumor retraction after induction chemotherapy (IC) combined with concurrent chemoradiotherapy (CCRT) for primary nasopharyngeal carcinoma (NPC) in non-endemic areas and to validate its efficacy. Methods: A total of 272 patients (155 in the training set, 66 in the internal validation set, and 51 in the external validation set) with biopsy pathologically confirmed primary NPC who were screened for pretreatment MRI were retrospectively collected. The NPC tumor was delineated as a region of interest in the two sequenced images of MRI before treatment and after IC, followed by radiomics feature extraction. With the use of maximum relevance minimum redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) algorithms, logistic regression was performed to establish pretreatment MRI radiomics and pre- and post-IC Delta radiomics models. The optimal Youden's index was taken; the receiver operating characteristic (ROC) curve, calibration curve, and decision curve were drawn to evaluate the predictive efficacy of different models. Results: Seven optimal feature subsets were selected from the pretreatment MRI radiomics model, and twelve optimal subsets were selected from the Delta radiomics model. The area under the ROC curve, accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the MRI radiomics model were 0.865, 0.827, 0.837, 0.813, 0.776, and 0.865, respectively; the corresponding indicators of the Delta radiomics model were 0.941, 0.883, 0.793, 0.968, 0.833, and 0.958, respectively. Conclusion: The pretreatment MRI radiomics model and pre- and post-IC Delta radiomics models could predict the IC-CCRT response of NPC in non-epidemic areas.

Case Report: A report on the countermeasures after the rupture of the scalp venous indwelling needle catheter in 12 cases.

As a substitute for a scalp needle, the intravenous indwelling needle is easy to operate and easy to use. it is not only conducive to the rescue of critically ill children, improves nursing efficiency, but also avoids pain caused by repeated venipuncture. However, cases of indwelling needle catheter breaking and remaining in scalp vessels are rarely reported. This study collected 12 cases of scalp vein indwelling needle rupture and retention in scalp vessels in our center from January 2012 to January 2022. It was found that there were 7 males and 5 females, with an average age of 19.17 ± 8.96 months. The average length of the severed end was 15.00 ± 1.54 mm. In 8 cases, the catheter was broken during the haircut, and in 2 cases, the wall structure was damaged and broken after repeated folding of the catheter. In 2 cases, the children did not cooperate during extubation, the head twisted violently and the catheter was broken.5 cases tried to extract it by manipulation and hemostatic forceps, of which 4 cases were successful, and 1 case was successfully removed after the completion of three-dimensional computerized tomography (3D-CT) imaging positioning. The remaining 7 cases were removed by operation, and the success rate of the first operation was 100% in 4 cases who chose 3D-CT. The other 3 cases chose ordinary CT plain scan positioning, the success rate of the first operation was 66.6%, and one child was successfully removed after the second operation after the failure of the operation plus 3D-CT scan positioning. All the children were in stable condition after the operation and were discharged smoothly. When the broken catheter is relatively shallow and the scalp is not completely closed, we could choose the preliminary positioning of B-ultrasound or ordinary CT, and then try to remove it by manual squeezing combined with hemostatic forceps. However B-ultrasound and ordinary CT could not meet the requirements of accurate location, 3D-CT has a very important localization value for surgery, which can improve the success rate and help successfully remove the ruptured catheter.

Superfine pulverisation pretreatment to enhance crystallinity of cellulose from Lycium barbarum L. leaves.

Superfine pulverisation (SFP) pretreatment of Lycium barbarum L. leaves was performed to obtain highly crystalline cellulose. Compared with other common pulverisation methods, SFP enhanced cellulosic crystallinity by 18.3 % and 8.4 %, with and without post-acid treatments, respectively. XRD and solid-state NMR analyses showed that SFP facilitated the exposure of amorphous substances (i.e., hemicellulose and lignin) to NaOH and H2O2. Large amounts of silicon (5.5 %) and aluminium (2.1 %) were found to incorporate into the crystalline regions of SFP-produced cellulose. Further FTIR and thermogravimetric analyses revealed that SFP-produced cellulose contained large amounts of hydroxyl groups, affecting the cellulosic crystallinity and thermal stability. These findings demonstrate the potential for SFP to serve as a green technology for production of highly crystalline and mineral-rich cellulose.

How Inclusive Leadership Enhances Follower Taking Charge: The Mediating Role of Affective Commitment and the Moderating Role of Traditionality.

PURPOSE: Leaders try to stimulate follower taking charge to promote organizational change and effectiveness in current increasingly complex and changing environment. Based on social identity theory, we developed a mediated moderation model in which affective commitment was theorized as a mediating mechanism underlining why followers feel motivated to taking charge with the supervision of inclusive leadership. Furthermore, traditionality should be a relevant boundary condition to moderate such a relationship in China. METHODS: There was three times lagged research conducted at the city of Shanghai, Shenzhen, and Nanjing. A series of valid questionnaires were accomplished by 246 participants, including the inclusive leadership, affective commitment, traditionality, and follower taking charge. Our model adopted hierarchical regression analysis to explore hypothesis. RESULTS: Inclusive leadership is positively related to affective commitment (ß= 0.589, p < 0.001). Affective commitment was positively related to follower taking charge (ß= 0.165, p < 0.01). Affective commitment mediates the relationship between inclusive leadership and taking charge with 95% bias-corrected confidence intervals [0.068, 0.233]. Interactive effect of affective commitment and traditionality on follower taking charge was also significant (ß=-0.189, p <0.001), and the effect of affective commitment on follower taking charge was more pronounced and positive with low (b = 0.361, p <0.001) rather than high (b =0.172, ns.) level of affective commitment. Moreover, the indirect effect of inclusive leadership on taking charge through affective commitment was significant when traditionality was low (b = 0.270, 95% CI = [0.179, 0.371]), the indirect effect became insignificant with high traditionality (b = 0.046, 95% CI = [-0.034, 0.123]). CONCLUSION: Our study shows that affective commitment mediates the relationship between inclusive leadership and follower taking charge. Moreover, the influence of affective commitment on follower taking charge was moderated by traditionality. Affective commitment was positively associated with taking charge only for followers with low traditionality. Additionally, the mediated moderation relationship between inclusive leadership and follower taking charge via affective commitment was stronger under low traditionality.

Comparative transcriptome analysis of two contrasting wolfberry genotypes during fruit development and ripening and characterization of the LrMYB1 transcription factor that regulates flavonoid biosynthesis.

BACKGROUND: Lycium barbarum and L. ruthenicum have been used as traditional medicinal plants in China and other Asian counties for centuries. However, the molecular mechanisms underlying fruit development and ripening, as well as the associated production of medicinal and nutritional components, have been little explored in these two species. RESULTS: A competitive transcriptome analysis was performed to identify the regulators and pathways involved in the fruit ripening of red wolfberry (L. barbarum) and black wolfberry (L. ruthenicum) using an Illumina sequencing platform. In total, 155,606 genes and 194,385 genes were detected in red wolfberry (RF) and black wolfberry (BF), respectively. Of them, 20,335, 24,469, and 21,056 genes were differentially expressed at three different developmental stages in BF and RF. Functional categorization of the differentially expressed genes revealed that phenylpropanoid biosynthesis, flavonoid biosynthesis, anthocyanin biosynthesis, and sugar metabolism were the most differentially regulated processes during fruit development and ripening in the RF and BF. Furthermore, we also identified 38 MYB transcription factor-encoding genes that were differentially expressed during black wolfberry fruit development. Overexpression of LrMYB1 resulted in the activation of structural genes for flavonoid biosynthesis and led to an increase in flavonoid content, suggesting that the candidate genes identified in this RNA-seq analysis are credible and might offer important utility. CONCLUSION: This study provides novel insights into the molecular mechanism of Lycium fruit development and ripening and will be of value to novel gene discovery and functional genomic studies.

Degradation of polysaccharides from Lycium barbarum L. leaves improves bioaccessibility and gastrointestinal transport of endogenous minerals.

Acidic heteropolysaccharide (LP) from Lycium barbarum L. leaves has compact globular structure which wrapped abundant endogenous minerals inside by ionic interactions with uronic acid. This study investigated the efficacy of chemical degradation of LP on the bioaccessibility and transport of endogenous minerals in simulated gastrointestinal fluids. Results showed that the degradation using vitamin C and hydrogen peroxide mildly decreased LP molecular weight from 162.0 kDa to 94.3 kDa, and the structure of degraded LP (LPD) was converted to loose coil. After the simulated intestinal digestion, the accessibility of Ca, Fe, Zn, and Mg in LPD increased by119%, 52%, 103% and 112.5% compared with the intact LP, respectively, and in particular, the uptake rate increased by 15.8%, 8.1%, 23.4% and 21.6% for Ca, Fe, Zn, and Mg, respectively. These results demonstrated that the chemical degradation is a helpful strategy to improve the uptake of endogenous minerals wrapped in polysaccharide.

miR-593-5p inhibit cell proliferation by targeting PLK1 in non small cell lung cancer cells.

Worldwide, lung cancer has the highest rates of mortality and morbidity, with the majority of its pathology attributable to non-small cell lung cancer (NSCLC). MicroRNAs are pivotal in the occurrence and development of cancer. However, the role of miRNA-593-5p in the progression of NSCLC is not clear. In this study, we investigate, in vitro, whether miRNA-593-5p inhibits NSCLC cell proliferation. To clarify its specific mechanism of inhibition, we used bioinformatics to predict its target genes and identified PLK1. Luciferase reporter assay confirmed the binding of miR-593-5p to the PLK1 3'-UTR in a sequence-specific manner in NSCLC cells. Additionally, we also found through Western blot and quantitative RT-PCR that miR-593-5p down-regulates the expression of PLK1 protein. Finally, PLK1 overexpression was shown to disinhibit NSCLC cell proliferation. Taken together, this evidence suggests that miR-593-5p inhibits NSCLC cell proliferation by inhibiting PLK1 expression.

Enhanced Biotransformation Productivity of Gamma-Decalactone from Ricinoleic Acid Based on the Expanded Vermiculite Delivery System.

Natural gamma-decalactone (GDL) produced by biotransformation is an essential food additive with a peach-like aroma. However, the difficulty of effectively controlling the concentration of the substrate ricinoleic acid (RA) in water limits the biotransformation productivity, which is a bottleneck for industrialization. In this study, expanded vermiculite (E-V) was utilized as a carrier of RA to increase its distribution in the medium. E-V and three commonly used organic compounds were compared with respect to their effects on the biotransformation process, and the mechanism was revealed. Scanning electron microscopy, Fourier transform infrared spectroscopy and thermogravimetric analysis indicated that RA was physically adsorbed onto the surface of and inside E-V instead of undergoing a chemical reaction, which increased the opportunity for interactions between microorganisms and the substrate. The highest concentration of GDL obtained in the medium with E-V was 6.2 g/l, which was 50% higher than that in the reference sample. In addition, the presence of E-V had no negative effect on the viability of the microorganisms. This study provides a new method for producing natural GDL through biotransformation on an industrial scale.

Degradation enhances the anticoagulant and antiplatelet activities of polysaccharides from Lycium barbarum L. leaves.

In the current study, a carboxyl-rich polysaccharide purified from Lycium barbarum L. leaves (hereafter, LP) and its degradation with ascorbic acid and hydrogen peroxide were characterized. Degradation decreased the molecular weight of LP from 4.63 × 104 to 3.45 × 104 Da, and increased its zeta potential from -8.01 to -5.35 mV. In vitro experiments showed that degradation significantly increased the anticoagulant activity and, in particular, antiplatelet activity of LP (p < 0.05). The polysaccharide with the highest degree of degradation had higher inhibitory activity than aspirin against arachidonic acid- and thrombin-induced platelet aggregation at 0.5 g/mL. A reduction in uronic acids between LP and its degradation products significantly decreased their antiplatelet activity (p < 0.05). Further analysis confirmed that polysaccharides changed from a compact spherical structure to a random coil in aqueous solution following degradation, which facilitated the interaction of polysaccharides and platelets.

Endogenous calcium attenuates the immunomodulatory activity of a polysaccharide from Lycium barbarum L. leaves by altering the global molecular conformation.

A heteropolysaccharide, LP5, was purified from Lycium barbarum L. leaves. It was identified as a calcium-rich polysaccharide (8.6 mg calcium/g) with a molecular weight of 2.50 × 105 Da. The polysaccharide was composed of six kinds of monosaccharides, of which mannose and xylose are the main components. And it contains 16.37% glucuronic acid. Studies on RAW264.7 cells demonstrated that this polysaccharide exhibited potent immunomodulatory activity, including an increase in phagocytic activity, as well as the release of both nitric oxide and cytokines. However, after the depletion of calcium, the polysaccharide exhibited greater immunomodulatory activity (p < 0.05). Further conformation analysis confirmed that the polysaccharide changed from a compact spherical conformation to a random coil structure in aqueous solution after the depletion of calcium, which resulted in increased immunomodulatory activity by LP5.