Microglia lactylation in relation to central nervous system diseases.

The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis. Microglia, as innate immune cells, play important roles in the maintenance of central nervous system homeostasis, injury response, and neurodegenerative diseases. Lactate has been considered a metabolic waste product, but recent studies are revealing ever more of the physiological functions of lactate. Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions, macrophage polarization, neuromodulation, and angiogenesis and has also been implicated in the development of various diseases. This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation, histone versus non-histone lactylation, and therapeutic approaches targeting lactate. Finally, we summarize the current research on microglia lactylation in central nervous system diseases. A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

Pro-resolving lipid mediator reduces amyloid-ß42-induced gene expression in human monocyte-derived microglia.

JOURNAL/nrgr/04.03/01300535-202503000-00031/figure1/v/2024-06-17T092413Z/r/image-tiff Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-ß. With this objective, we analyzed the relevance of human monocyte-derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-ß42-induced Alzheimer's disease-like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease-like neuroinflammation in human brain microglia after incubation with amyloid-ß42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-ß42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-ß42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-ß42-induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.

Adsorption of typical NDMA precursors by superfine powdered activated carbon: Critical role of particle size reduction.

Control of N-nitrosodimethylamine (NDMA) in drinking water could be achieved by removing its precursors as one practical way. Herein, superfine powdered activated carbons with a diameter of about 1 µm (SPACs) were successfully prepared by grinding powdered activated carbon (PAC, D50=24.3 µm) and applied to remove model NDMA precursors, i.e. ranitidine (RAN) and nizatidine (NIZ). Results from grain diameter experiments demonstrated that the absorption velocity increased dramatically with decreasing particle size, and the maximum increase in k2 was 26.8-folds for RAN and 33.4-folds for NIZ. Moreover, kinetic experiments explained that rapid absorption could be attributed to the acceleration of intraparticle diffusion due to the shortening of the diffusion path. Furthermore, performance comparison experiments suggested that the removal of RAN and NIZ (C0=0.5 mg/L) could reach 61.3% and 60%, respectively, within 5 min, when the dosage of SAPC-1.1 (D50=1.1 µm) was merely 5 mg/L, while PAC-24.3 could only eliminate 17.5% and 18.6%. The adsorption isotherm was well defined by Langmuir isotherm model, indicating that the adsorption of RAN/NIZ was a monolayer coverage process. The adsorption of RAN or NIZ by SAPC-1.1 and PAC-24.3 was strongly pH dependent, and high adsorption capacity could be observed under the condition of pH > pka+1. The coexistence of humic acid (HA) had no significant effect on the adsorption performance because RAN/NIZ may be coupled with HA and removed simultaneously. The coexistence of anions had little effect on the adsorption also. This study is expected to provide an alternative strategy for drinking water safety triggered by NDMA.

Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202505000-00029/figure1/v/2024-07-28T173839Z/r/image-tiff Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties. A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury. A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity, and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar, thus limiting axonal reentry into the host spinal cord. Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury. We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders, Schwann cells migrated for considerable distances in both rostral and caudal directions. Such Schwann cell migration led to enhanced axonal regrowth, including the serotonergic and dopaminergic axons originating from supraspinal regions, and promoted recovery of locomotor and urinary bladder functions. Importantly, the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury, even when treatment was delayed for 3 months to mimic chronic spinal cord injury. These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

Multilayered hydrogel scaffold construct with native tissue matched elastic modulus: A regenerative microenvironment for urethral scar-free healing.

The unsuitable deformation stimulus, harsh urine environment, and lack of a regenerative microenvironment (RME) prevent scaffold-based urethral repair and ultimately lead to irreversible urethral scarring. The researchers clarify the optimal elastic modulus of the urethral scaffolds for urethral repair and design a multilayered PVA hydrogel scaffold for urethral scar-free healing. The inner layer of the scaffold has self-healing properties, which ensures that the wound effectively resists harsh urine erosion, even when subjected to sutures. In addition, the scaffold's outer layer has an extracellular matrix-like structure that synergizes with adipose-derived stem cells to create a favorable RME. In vivo experiments confirm successful urethral scar-free healing using the PVA multilayered hydrogel scaffold. Further mechanistic study shows that the PVA multilayer hydrogel effectively resists the urine-induced inflammatory response and accelerates the transition of urethral wound healing to the proliferative phase by regulating macrophage polarization, thus providing favorable conditions for urethral scar-free healing. This study provides mechanical criteria for the fabrication of urethral tissue-engineered scaffolds, as well as important insights into their design.

Traditional uses, botany, phytochemistry, pharmacology and applications of Labisia pumila: A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Labisia pumila (Blume) Fern.-Vill, also known as Kacip Fatimah, is a traditional medicinal herb common throughout Southeast Asia. It is primarily used to facilitate childbirth and postpartum recovery in women. Additionally, it can also be used to treat dysentery, rheumatism, gonorrhea, and as an anti-flatulent. AIM OF THIS REVIEW: This article aims to provide a comprehensive review of the traditional uses, botany, cultivation, phytochemistry, pharmacological effects, practical applications, and potential uses of L. pumila (LP). Furthermore, we also explore the safety of this plant and its potential prospects for application. MATERIALS AND METHODS: The keywords "Labisia pumila," "Kacip Fatimah," and "Marantodes pumilum" were used to collect relevant information through electronic searches (including Elsevier, PubMed, Google Scholar, Baidu Scholar, CNKI, ScienceDirect, and Web of Science). RESULTS: This review summarizes 102 chemical components from different parts of the plant, including flavonoids, phenolic acids, saponins, and other chemical components. In addition, we also address the associated cultivation conditions, traditional uses, pharmacological effects and toxicity. A large number of reports indicate that LP has various pharmacological effects such as antioxidant, phytoestrogenic, anti-inflammtory, antimicrobial, anti-osteoporosis and anti-obesity properties. These results provide valuable references for future research on LP. In addition, LP is also a potential medicinal and edible plant, and is currently sold on the market as a dietary supplement. CONCLUSIONS: LP is a renowned traditional ethnic medicine with numerous pharmacological activities attributed to its bioactive components. Therefore, isolation and identification of the chemical components in LP can be a focus of our future research. Current studies have focused only on the effects of LP on estrogen deficiency-related diseases in women and bone diseases. There is no scientific evidence for other traditional uses. Therefore, it is important to further explore its pharmacological activities and fill the research gaps related to other traditional uses. Furthermore, research on its safety should be expanded to prepare clinical applications.

Systematic metabolic engineering enables highly efficient production of vitamin A in Saccharomyces cerevisiae.

Vitamin A is a micronutrient critical for versatile biological functions and has been widely used in the food, cosmetics, pharmaceutical, and nutraceutical industries. Synthetic biology and metabolic engineering enable microbes, especially the model organism Saccharomyces cerevisiae (generally recognised as safe) to possess great potential for the production of vitamin A. Herein, we first generated a vitamin A-producing strain by mining ß-carotene 15,15'-mono(di)oxygenase from different sources and identified two isoenzymes Mbblh and Ssbco with comparable catalytic properties but different catalytic mechanisms. Combinational expression of isoenzymes increased the flux from ß-carotene to vitamin A metabolism. To modulate the vitamin A components, retinol dehydrogenase 12 from Homo sapiens was introduced to achieve more than 90 % retinol purity using shake flask fermentation. Overexpressing POS5Δ17 enhanced the reduced nicotinamide adenine dinucleotide phosphate pool, and the titer of vitamin A was elevated by almost 46 %. Multi-copy integration of the key rate-limiting step gene Mbblh further improved the synthesis of vitamin A. Consequently, the titer of vitamin A in the strain harbouring the Ura3 marker was increased to 588 mg/L at the shake-flask level. Eventually, the highest reported titer of 5.21 g/L vitamin A in S. cerevisiae was achieved in a 1-L bioreactor. This study unlocked the potential of S. cerevisiae for synthesising vitamin A in a sustainable and economical way, laying the foundation for the commercial-scale production of bio-based vitamin A.

The impact of plan complexity on calculation and measurement-based pre-treatment verifications for sliding-window intensity-modulated radiotherapy.

Background and purpose: In sliding-window intensity-modulated radiotherapy, increased plan modulation often leads to increased plan complexities and dose uncertainties. Dose calculation and/or measurement checks are usually adopted for pre-treatment verification. This study aims to evaluate the relationship among plan complexities, calculated doses and measured doses. Materials and methods: A total of 53 plan complexity metrics (PCMs) were selected, emphasizing small field characteristics and leaf speed/acceleration. Doses were retrieved from two beam-matched treatment devices. The intended dose was computed employing the Anisotropic Analytical Algorithm and validated through Monte Carlo (MC) and Collapsed Cone Convolution (CCC) algorithms. To measure the delivered dose, 3D diode arrays of various geometries, encompassing helical, cross, and oblique cross shapes, were utilized. Their interrelation was assessed via Spearman correlation analysis and principal component linear regression (PCR). Results: The correlation coefficients between calculation-based (CQA) and measurement-based verification quality assurance (MQA) were below 0.53. Most PCMs showed higher correlation rpcm-QA with CQA (max: 0.84) than MQA (max: 0.65). The proportion of rpcm-QA  ≥ 0.5 was the largest in the pelvis compared to head-and-neck and chest-and-abdomen, and the highest rpcm-QA occurred at 1 %/1mm. Some modulation indices for the MLC speed and acceleration were significantly correlated with CQA and MQA. PCR's determination coefficients (R2 ) indicated PCMs had higher accuracy in predicting CQA (max: 0.75) than MQA (max: 0.42). Conclusions: CQA and MQA demonstrated a weak correlation. Compared to MQA, CQA exhibited a stronger correlation with PCMs. Certain PCMs related to MLC movement effectively indicated variations in both quality assurances.

Discovery of natural product derivative triptolidiol as a direct NLRP3 inhibitor by reducing K63-specific ubiquitination.

BACKGROUND AND PURPOSE: NLRP3 is up-regulated in inflammatory and autoimmune diseases. The development of NLRP3 inhibitors is challenged by the identification of compounds with distinct mechanisms of action avoiding side effects and toxicity. Triptolide is a natural product with multiple anti-inflammatory activities, but a narrow therapeutic window. EXPERIMENTAL APPROACH: Natural product triptolide derivatives were screened for NLRP3 inhibitors in human THP-1 and mouse bone marrow-derived macrophages. The efficacy of potent NLRP3 inhibitors was evaluated in LPS-induced acute lung injury and septic shock models. KEY RESULTS: Triptolidiol was identified as a selective inhibitor of NLRP3 with high potency. Triptolidiol inactivated the NLRP3 inflammasome in human THP-1 and mouse primary macrophages primed with LPS. Triptolidiol specifically inhibited pro-caspase 1 cleavage downstream of NLRP3, but not AIM2 or NLRC4 inflammasomes. Based on the structure-activity relationship study, the C8-ß-OH group was critical for its binding to NLRP3. Triptolidiol exhibited a submicromolar KD for NLRP3, binding to residue C280. This binding prevented the interaction of NLRP3 with NEK7, the key regulator of NLRP3 inflammasome oligomerization and assembly, but not with the inflammasome adaptor protein ASC. Triptolidiol decreased the K63-specific ubiquitination of NLRP3, leading NLRP3 to a "closed" inactive conformation. Intraperitoneal administration of triptolidiol significantly attenuated LPS-induced acute lung injury and lethal septic shock. CONCLUSION AND IMPLICATIONS: Triptolidiol is a novel NLRP3 inhibitor that regulates inflammasome assembly and activation by decreasing K63-linked ubiquitination. Triptolidiol has novel structural features that make it distinct from reported NLRP3 inhibitors and represents a viable therapeutic lead for inflammatory diseases.

Overlooked Trace Molecules in Organic Aerosol Revealed by Gas Chromatography-Orbitrap Mass Spectrometry.

Molecular characterization of organic aerosol (OA) is crucial for understanding its sources and atmospheric processes. However, the chemical components of OA remain not well constrained. This study used gas chromatography-Orbitrap mass spectrometry (GC-Orbitrap MS) and GC-Quadrupole MS (GC-qMS) to investigate the organic composition in PM2.5 from Xi'an, Northwest China. GC-Orbitrap MS identified 335 organic tracers, including overlooked isomers and low-concentration molecules, approximately 1.6 times more than GC-qMS. The "molecular corridor" assessment shows the superior capability of GC-Orbitrap MS in identifying an expansive range of compounds with higher volatility and oxidation states, such as furanoses/pyranoses, di/hydroxy/ketonic acids, di/poly alcohols, aldehydes/ketones, and amines/amides. Seasonal variations in OA composition reflect diverse sources: increased di/poly alcohols in winter are derived from indoor emissions, furanoses/pyranoses and heterocyclics in spring and summer might be from biogenic emissions and secondary formation, and amides in autumn are probably from biomass burning. Integrating partial least squares discriminant analysis (PLS-DA) and potential source contribution function (PSCF) models, the source similarities and differences are further elucidated, highlighting the role of local emissions and transport from southern cities. This study offers new insights into the OA composition aided by the high mass resolution and sensitivity of GC-Orbitrap MS.

PSMD2 overexpression as a biomarker for resistance and prognosis in renal cell carcinoma treated with immune checkpoint and tyrosine kinase inhibitors.

BACKGROUND: Integrated immune checkpoint inhibitors (ICIs) plus tyrosine kinase inhibitors (TKIs) are now the recommended first-line therapy to manage renal cell carcinoma (mRCC). Proteasome 26S subunit non-ATPase 2 (PSMD2) overexpression in tumors has been correlated with tumor progression. Currently, mRCC lacks an established biomarker for the combination of ICI+TKI. METHODS: This study involved RNA sequencing of RCC patients from two cohorts treated with ICI+TKI (ZS-MRCC and JAVELIN-Renal-101). We utilized immunohistochemistry alongside flow cytometry, aiming at assessing immune cell infiltration and functionality in high-risk localized RCC samples. Response and progression-free survival (PFS) were evaluated relying upon RECIST criteria. RESULTS: PSMD2 was significantly overexpressed in advanced RCC and among non-responders to ICI+TKI therapy. Overexpressed PSMD2 was correlated with poor PFS in the ZS-MRCC and JAVELIN-101 cohorts. Multivariate Cox analysis validated PSMD2 as an independent PFS predictor. PSMD2 overexpression was related to a reduction in CD8+ T cells, especially GZMB+ CD8+ T cells, besides an increase in PD1+ CD4+ T cells. Additionally, tumors with high PSMD2 levels showed enhanced T cell exhaustion levels and a higher regulatory T cell presence. A Machine Learning (ML) model based on PSMD2 expression and other screened factors was subsequently developed to predict the effectiveness of ICI+TKI. CONCLUSIONS: Elevated PSMD2 expression is linked to resistance and decreased PFS in mRCC patients undergoing ICI+TKI therapy. High PSMD2 levels are also associated with impaired function and increased exhaustion of tumor-infiltrating lymphocytes. An ML model incorporating PSMD2 expression could potentially identify patients who may have a higher likelihood of benefiting from ICI+TKI.

Multi-win situation of wastewater purification, carbon emission reduction and resource utilization: Conversion of refractory organics and nitrate to urea and ammonia in a flow-through electrochemical integrated system.

The advanced oxidation process is an efficient technology for the degradation and detoxification of refractory organics to ensure water safety. However, most researches focus on improving pollutant degradation but overlook carbon emission and resource utilization. In this study, a flow-through electrochemical integrated system was constructed to simultaneously realize bisphenol A (BPA) oxidation into small non-toxic organics and CO2, and generated CO2 coupled with nitrate-containing wastewater conversion to urea and ammonia on a porous cathode (Zr-Fe/CN). The synergistic effect between anodic BPA oxidation with cathodic CO2 and NO3-reduction improves the electron utilization efficiency and thus increasing the BPA degradation, urea yield rate (UYR) and NH3 yield rate (NYR) by 13.4 % 18.4 % and 8.3 %, respectively. Furthermore, the flow-through operation mode significantly increased the mass transfer efficiency and quickly carried generated CO2 from the anode into the cathode to improve CO2 utilization efficiency. Compared to the parallel plate electrode reactor, the BPA degradation efficiency, UYR and NYR in the flow-through reactor increased from 59.46 % to 84.49 % (the initial concentration of BPA was 40 mg/L), 9.94 mmol h-1g-1 to 19.55 mmol h-1g-1, and 80.31 mmol h-1g-1 to 106.06 mmol h-1g-1 within 60 min, respectively. Moreover, the total carbon conversion efficiency (from BPA to urea) increased from 20.2 % to 42.4 % and the total Faraday efficiency (FE) increased from 78.6 % to 96.3 %. This work provides a multi-win strategy of harmless, resource-based and carbon emission reduction for wastewater treatment.

Seno-antigen-pulsed dendritic cell vaccine induce anti-aging immunity to improve adipose tissue senescence and metabolic abnormalities.

Anti-aging immunity induced by vaccines was recently reported to enable the elimination of senescent cells. However, the initial immune response to vaccination declines with age, and there is evidence that elderly dendritic cells (DCs) have a reduced capacity to stimulate T cells. Identification of alternative anti-aging vaccine is therefore warranted. Here, we developed a DC vaccine that delivers a cationic protein (CP) fused with the seno-antigen peptides Gpnmb (Gpnmb-CP) into DCs. The Gpnmb-CP-pulsed DC vaccine (Gpnmb-CP-DC) efficiently presented antigens and activated CD8+ T cells, leading to enhanced immune cytotoxicity and memory responses in CD8+ T cells. Thus, the targeted anti-aging immunity triggered by Gpnmb-CP-DC has the ability to selectively eliminate senescent adipocytes and effectively improve age-related metabolic abnormalities in both high-fat diet (HFD)-induced young and aged mice models, as well as in natural aging mouse model. In contrast, the Gpnmb-CP protein vaccine exhibits minimal efficacy in aged mice model. Furthermore, we observed a decreased phagocytic capacity for antigens in aging DCs, accompanied by an upregulation of the immune checkpoint PDL1 expression and a noticeable decline in activated CD8+ T cell. Hence, Gpnmb-CP-DC emerges as a promising vaccine candidate, demonstrating the capacity to induce potent anti-aging immunity, mitigating adipose tissue senescence and metabolic abnormalities, while resilient to the senescent environment of the organism.

The causal link between nitrogen structure and physiological processes of Ulva prolifera as the causative species of green tides.

Harmful algal blooms (HABs) increase with eutrophication depending on the nutrient structure (availability and ratios), but an unequivocal causal link between these factors is rarely established. Here, we provide support for the causal link between the nitrogen structure and physiological processes of Ulva prolifera as the causative species of Yellow Sea green tides (YSGTs) using in situ and laboratory experiments. The results showed that the components of nitrogen nutrients in seawater exhibited significant spatiotemporal variation. The concentration of NO3--N showed a notable decreasing trend from south to north. Sufficient dissolved inorganic nitrogen (DIN) induced increases in thalli nitrate reductase (NR) and glutamine synthetase (GS) activities. This could accelerate thalli uptake of nitrogen nutrients. The glutamate dehydrogenase (GDH) activity was significantly upregulated with the increasing proportion of dissolved organic nitrogen (DON) in seawater. The change in nitrogen structure regulated the activity of NR during the long-distance floating migration of the YSGTs. And the activity of NR could modulate the nitric oxide (NO) content in the thalli. NO was used as a signal molecule to enhance the antioxidant defense system of thalli. The efficient antioxidant system in the thalli could reduce oxidative stress and effectively maintain high photosynthetic activity. The findings deepen our understanding of the relationship between nitrogen structures and key biological processes in macroalgae. This study also suggest that NO can enhance key biological processes in U. prolifera under varying nitrogen structures.

Metagenomic insights into the mechanistic differences of plant polyphenols and nitrocompounds in reducing methane emissions using the rumen simulation technique.

Methane (CH4) emissions from ruminants contribute significantly to greenhouse gas levels and also result in considerable feed energy losses. Plant polyphenols and nitrocompounds are two typical types of methane inhibitors. The study investigates the mechanistic differences between 2-nitroethanol (NE) and proanthocyanidins (PAC) in reducing methane emissions from ruminant livestock using the rumen simulation technique (RUSITEC) combined with metagenomic analyses. The experiment was performed as a complete randomized block design with 3 runs. Run was used as a blocking factor. The treatments included a control (CON) with no additive, NE at 0.5 g/kg dry matter (DM), and PAC at 20 g/kg DM, all incubated in vitro for 24 h (h) with eight replicates per treatment. The results showed that NE significantly reduced CH4 production by 94.9 % (P < 0.01) and total volatile fatty acid (TVFA) concentration by 11.1 % (P < 0.05) compared to the control. NE also decreased the acetate-to-propionate ratio (A/P) from 1.93 to 1.60 (P < 0.01), indicating a shift towards more efficient fermentation. In contrast, PAC reduced methane production by 11.7 % (P < 0.05) and decreased the A/P (P < 0.05) while maintaining microbial diversity and fermentation stability, with no significant impact on TVFA concentration (P > 0.05). Metagenomic analysis revealed that NE markedly suppressed the abundance of key genera involved in carbohydrate metabolism, including Prevotella and Bacteroides, leading to reduced acetate and butyrate pathways. NE also selectively inhibited methanogenic archaea, particularly Methanobrevibacter spp., which are integral to the hydrogenotrophic pathway (P < 0.01). On the other hand, PAC showed selective inhibition of Methanosphaera spp., targeting the methylotrophic pathway (P < 0.01). These findings provide valuable insights into the distinct microbial and metabolic pathways modulated by NE and PAC, offering potential strategies for developing effective dietary interventions to mitigate methane emissions in ruminant livestock.

Insights into the fabrication and antibacterial effect of fibrinogen hydrolysate-carrageenan loading apigenin and quercetin composite hydrogels.

Escherichia coli and Staphylococcus aureus are the most prevalent pathogenic bacteria, often resulting in the foodborne disease outbreaks through food spoilage and foodborne infections. To prevent and control food spoilage and foodborne infections induced by Escherichia coli and Staphylococcus aureus, the antibacterial hydrogels were fabricated using fibrinogen hydrolysate-carrageenan (AHs-C) and flavonoids (apigenin and quercetin), and the antibacterial effect of the composite hydrogels against Escherichia coli and Staphylococcus aureus was further investigated. The results of mechanical property exhibited that the composite hydrogels with 0.2 % of apigenin and quercetin (AHs-C-Ap/Que) showed the highest hardness and swelling property compared with the separate addition of apigenin or quercetin. Scanning electron microscopy and atomic force microscopy showed that the dense networks were formed in the hydrogels of AHs-C-Ap/Que., and the average roughness of AHs-C-Ap/Que. significantly increased to 30.70 nm compared with AHs-C. 1H NMR and FTIR spectra demonstrated that apigenin and quercetin were bound to AHs-C by hydrogen bond, hydrophobic interaction and Schiff base, where the interactions between Ap/Que. and AHs-C was stronger compared with the separate addition of apigenin or quercetin. The hydrogels of AHs-C-Ap/Que. showed the highest antibacterial capacity and antibacterial adhesion against Escherichia coli and Staphylococcus aureus. The antibacterial adhesion assay showed that 99 % removal ratios for E. coli and S. aureus were observed in AHs-C-Ap/Que. hydrogels, which showed a great potential to prevent food spoilage and foodborne infections.

Prognostic significance of serum secreted frizzled-related protein 5 in patients with acute aortic dissection.

Background: Secreted frizzled-related protein 5 (SFRP5) is a novel adipokine that has been found to be closely associated with metabolic and cardiovascular diseases. We investigated serum SFRP5 levels during the acute phase and their predictive value for the prognosis of acute aortic dissection (AAD). Methods: In total, 152 AAD patients and 164 controls were enrolled in this study. Serum SFRP5 levels were measured using an enzyme-linked immunosorbent assay (ELISA). AAD patients were divided into high-SFRP5 and low-SFRP5 groups based on the optimal cutoff value and followed up for prognosis. The primary endpoint was all-cause mortality, and the secondary endpoint focused on AAD-related events (including AAD-related mortality and unplanned reoperations). Results: Serum SFRP5 levels were significantly higher in AAD patients than in non-AAD controls, regardless of whether they had Stanford type A or B AD. Multivariate logistic regression analysis revealed an independent association between SFRP5 and the presence of AAD (adjusted OR 1.267, 95 % CI 1.152-1.394; p < 0.001). The receiver operating characteristic curve demonstrated that the optimal cutoff value for SFRP5 to predict the presence of AAD was 10.26 ng/mL (AUC 0.7241, sensitivity 49.34 %, specificity 87.20 %). Notably, serum SFRP5 levels of patients in the death group were significantly higher than those in the survival group. Compared with patients in the low-SFRP5 group, those in the high-SFRP5 group exhibited a significantly increased risk of all-cause mortality (HR 9.540, 95 % CI 2.803-32.473; p < 0.001) and AAD-related events (HR 6.915, 95 % CI 2.361-20.254; p < 0.001) during the follow-up period. Conclusion: Serum SFRP5 levels were significantly elevated in the acute phase of AAD, and high serum SFRP5 levels were independently associated with poor AAD prognosis. These results suggest that serum SFRP5 level during the acute phase may be an effective biomarker and therapeutic target for the prognosis of AAD.

Efficacy and safety of oral sodium bicarbonate in kidney-transplant recipients and non-transplant patients with chronic kidney disease: a systematic review and meta-analysis.

Introduction: We investigated the efficacy and safety of oral sodium bicarbonate in kidney-transplant recipients and non-transplant patients with chronic kidney disease (CKD), which are currently unclear. Methods: PubMed, Cochrane Library, Embase, and Web of Science were searched for randomized controlled trials investigating the efficacy and safety of sodium bicarbonate versus placebo or standard treatment in kidney-transplant and non-transplant patients with CKD. Results: Sixteen studies of kidney-transplant recipients (two studies, 280 patients) and non-transplant patients with CKD (14 studies, 1,380 patients) were included. With non-transplant patients, sodium bicarbonate slowed kidney-function declines (standardized mean difference [SMD]: 0.49, 95% confidence interval [CI]: 0.14-0.85, p = 0.006) within ≥12 months (SMD: 0.75 [95% CI: 0.12-1.38], p = 0.02), baseline-serum bicarbonate <22 mmol/L (SMD: 0.41 [95% CI: 0.19-0.64], p = 0.0004) and increased serum-bicarbonate levels (mean difference [MD]: 2.35 [95% CI: 1.40-3.30], p < 0.00001). In kidney-transplant recipients, sodium bicarbonate did not preserve graft function (SMD: -0.07 [95% CI: -0.30-0.16], p = 0.56) but increased blood pH levels (MD: 0.02 [95% CI: 0.00-0.04], p = 0.02). No significant adverse events occurred in the kidney-transplant or non-transplant patients (risk ratio [RR]: 0.89, [95% CI: 0.47-1.67], p = 0.72; and RR 1.30 [95% CI: 0.84-2.00], p = 0.24, respectively). However, oral sodium bicarbonate correlated with increased diastolic pressure and worsened hypertension and edema (MD: 2.21 [95% CI: 0.67-3.75], p = 0.005; RR: 1.44 [95% CI: 1.11-1.88], p = 0.007; and RR: 1.28 [95% CI: 1.00-1.63], p = 0.05, respectively). Discussion: Oral sodium bicarbonate may slow kidney-function decline in non-transplant patients with CKD taking sodium bicarbonate supplementation for ≥12 months or a baseline serum bicarbonate level of <22 mmol/L, without preserving graft function in kidney-transplant recipients. Sodium bicarbonate may increase diastolic pressure, and elevate a higher incidence of worsening hypertension and edema. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023413929.

Cyclosporine-induced alopecia:a case report, FDA adverse event reporting system analysis and literature assessment.

Cyclosporine is a potent immunosuppressive drug for various immune-mediated diseases in children. Cyclosporine's expected therapeutic effect also carries a wide range of side effects. One of the most common and intriguing dermatological side effects is hypertrichosis. However, recent reports have recognized alopecia as a potential adverse effect of cyclosporine. Here, we report a case of a 29-month-old boy diagnosed with aplastic anemia. During cyclosporine therapy, the patient presented with hair loss on the scalp, which and subsequently spread to the eyebrows and eyelashes. The alopecic symptoms were not relieved following topical minoxidil liniment interventions. When the cyclosporine was discontinued, a remarkable improvement was observed in the scalp, with complete hair regrowth. Data concerning cyclosporine from the FDA Adverse Event Reporting System (FAERS) database were extracted from January 2004 to January 2023. Within FAERS, our post-marketing pharmacovigilance analysis detected the reporting association of cyclosporine and alopecia. In monotherapy, cyclosporine-induced alopecia was observed in 118 cases, and tacrolimus-induced alopecia signals were detected in 197 cases. Although the potential mechanism of medication-induced hair loss is unclear, we identified a potential correlation between alopecia and cyclosporine, and it is still necessary to adequately recognize and clinically monitor this paradoxical reaction.