Present status of scheduled vaccinations and vaccination-related bleeding in Chinese children with haemophilia.

AIM: Many countries have detailed recommendations for haemophilia patients to reduce the risk of vaccination-related bleeding. However, data from developing countries are lacking. We investigated scheduled vaccinations and vaccination-related bleeding complications in Chinese children with haemophilia and analysed issues related to vaccinations. METHODS: Children with haemophilia in the PUMCH Haemophilia Treatment Centre were contacted via telephone. We distributed a vaccination questionnaire to their parents. The severity of haemophilia, coagulation factor infusions before vaccination, injection mode, and vaccination-related complications were analysed. RESULTS: A total of 440 valid questionnaires were received from 27 of 34 provinces in China. 31.3% (138/440) of the children with haemophilia did not receive all of their vaccinations. Among the children who received vaccinations, 48.1% (197/409) experienced bleeding complications. In patients with severe haemophilia, those on regular prophylaxis had a lower incidence of local hematoma compared to those on intermittent or no prophylaxis (14.3% vs. 26.5% vs. 39.7%, P < 0.05). The incidence of local hematomas was lower by subcutaneous (SQ) injections than by intramuscular injections (24.6% vs. 35.3%, P < 0.05). CONCLUSION: The vaccination rate is quite insufficient in Chinese children with haemophilia. Missed vaccinations are related to vaccination-related bleeding complications. Prophylaxis before vaccination and SQ injections would help reduce bleeding complications.

The effects of environmental factors on the synthesis of water-soluble Monascus red pigments via submerged fermentation: a review.

Monascus pigments (MPs) have been used as natural food pigments for many years. There is a high demand for Monascus red pigments (MRPs) to enhance color and for antibacterial and cancer prevention therapies in food and medicine. Most MRPs are not water soluble, and the yield of water-soluble MRPs is naturally low. On the other hand, water-soluble MRP is more cost effective for application in industrial mass production. Therefore, it is important to improve the yield of water-soluble MRPs. Environmental factors have a significant influence on the synthesis of water-soluble MRPs, which is crucial for the development of industrial production of water-soluble MRPs. This review introduces the biosynthetic pathways of water-soluble MRPs and summarizes the effects of environmental factors on the yield of water-soluble MRPs. Acetyl coenzyme A (acetyl-CoA) is a precursor for MPs synthesis. Carbon and nitrogen sources and the carbon/nitrogen ratio can impact MP production by regulating the metabolic pathway of acetyl-CoA. Optimization of fermentation conditions to change the morphology of Monascus can stimulate the synthesis of MPs. The appropriate choice of nitrogen sources and pH values can promote the synthesis of MRPs from MPs. Additives such as metal ions and non-ionic surfactants can affect the fluidity of Monascus cell membrane and promote the transformation of MRPs into water-soluble MRPs. This review will lay the foundation for the industrial production of water-soluble MRPs. © 2024 Society of Chemical Industry.

Fine Mapping of Five Grain Size QTLs Which Affect Grain Yield and Quality in Rice.

Grain size is a quantitative trait with a complex genetic mechanism, characterized by the combination of grain length (GL), grain width (GW), length to width ration (LWR), and grain thickness (GT). In this study, we conducted quantitative trait loci (QTL) analysis to investigate the genetic basis of grain size using BC1F2 and BC1F2:3 populations derived from two indica lines, Guangzhan 63-4S (GZ63-4S) and TGMS29 (core germplasm number W240). A total of twenty-four QTLs for grain size were identified, among which, three QTLs (qGW1, qGW7, and qGW12) controlling GL and two QTLs (qGW5 and qGL9) controlling GW were validated and subsequently fine mapped to regions ranging from 128 kb to 624 kb. Scanning electron microscopic (SEM) analysis and expression analysis revealed that qGW7 influences cell expansion, while qGL9 affects cell division. Conversely, qGW1, qGW5, and qGW12 promoted both cell division and expansion. Furthermore, negative correlations were observed between grain yield and quality for both qGW7 and qGW12. Nevertheless, qGW5 exhibited the potential to enhance quality without compromising yield. Importantly, we identified two promising QTLs, qGW1 and qGL9, which simultaneously improved both grain yield and quality. In summary, our results laid the foundation for cloning these five QTLs and provided valuable resources for breeding rice varieties with high yield and superior quality.

Vertical Cross-Alignments of 2D Semiconductors with Steered Internal Electric Field for Urea Electrooxidation via Balancing Intermediates Adsorption.

Single-component electrocatalysts generally lead to unbalanced adsorption of OH- and urea during urea oxidation reaction (UOR), thus obtaining low activity and selectivity especially when oxygen evolution reaction (OER) competes at high potentials (>1.5 V). Herein, a cross-alignment strategy of in situ vertically growing Ni(OH)2 nanosheets on 2D semiconductor g-C3N4 is reported to form a hetero-structured electrocatalyst. Various spectroscopy measurements including in situ experiments indicate the existence of enhanced internal electric field at the interfaces of vertical Ni(OH)2 and g-C3N4 nanosheets, favorable for balancing adsorption of reaction intermediates. This heterojunction electrocatalyst shows high-selectivity UOR compared to pure Ni(OH)2, even at high potentials (>1.5 V) and large current density. The computational results show the vertical heterojunction could steer the internal electric field to increase the adsorption of urea, thus efficiently avoiding poisoning of strongly adsorbed OH- on active sites. A membrane electrode assembly (MEA)-based electrolyzer with the heterojunction anode could operate at an industrial-level current density of 200 mA cm-2. This work paves an avenue for designing high-performance electrocatalysts by vertical cross-alignments of active components.

The improved aquila optimization approach for cost-effective design of hybrid renewable energy systems.

The growing demand for renewable energy systems is driven by climate change concerns, government support, technological advancements, economic viability, and energy security. These factors combine to create a strong momentum towards a clean and sustainable energy future. Governments, governments, and individuals are increasingly aware of the environmental impacts of traditional energy sources and adopting renewable energy solutions. Hybrid Renewable Energy Systems (HRES) are developed as an effective way of meeting the energy demands in remote locations. The complexity of the system components and the fluctuation of renewable energy sources make it difficult to design an economical and effective HRES. In this study, the Improved Aquila Optimization (IAO) approach has been suggested as a powerful tool to optimize the HRES design. The study addresses the implementation of the IAO approach in the design of HRES and emphasizes its advantages over other optimization techniques. Through extensive simulations and analyses, our findings demonstrate the superior performance of the IAO algorithm in improving the efficiency and cost-effectiveness of HRES. The optimization process using IAO resulted in a significant reduction in overall system costs, achieving an estimated Net Present Cost (NPC) of $201,973. It translates to a cost reduction of 25% compared to conventional optimization techniques. Furthermore, our analysis reveals that the IAO approach enhances the utilization of renewable energy sources, leading to a 15% increase in overall energy generation efficiency. These results highlight the effectiveness of the IAO approach in addressing the challenges associated with designing HRES. By significantly reducing costs and improving efficiency, it facilitates the adoption of sustainable energy systems in remote areas. The outcomes of this study emphasize the importance of utilizing advanced optimization techniques, such as IAO, to ensure the economic viability and environmental sustainability of HRES.

Asperustins A-J: Austocystins with Immunosuppressive and Cytotoxic Activities from Aspergillus ustus NRRL 5856.

Ten new (1-10) and nine known (11-19) austocystins, along with four known anthraquinones (20-23), were isolated from the culture of Aspergillus ustus NRRL 5856 by bioactivity-guided fractionation. The structures of the new compounds were elucidated by spectroscopic data analysis, X-ray crystallographic study, the modified Mosher's method, [Rh2(OCOCF3)4]-induced ECD spectral analysis, and comparison of the experimental ECD spectra with those of the similar analogues. Compounds 1-8 represent the first examples of austocystins with a C-4' oxygenated substitution. The absolute configuration of 1″-hydroxy austocystin D (11) was determined by single-crystal X-ray diffraction and consideration of its biosynthetic origin. Compounds 5, 9, and 11 exhibited significant inhibitory effects against the proliferation of ConA-induced T cells with IC50 values of 1.1, 1.0, and 0.93 µM, respectively. Furthermore, these compounds suppressed the expression of IL-6 in a dose-dependent manner. Compounds 10-12 and 14 showed pronounced cytotoxicities against MCF-7 with IC50 values of 3.9, 1.3, 0.46, and 2.3 µM, respectively.

Deep eutectic solvents pretreatment enhances methane production from anaerobic digestion of waste activated sludge: Effectiveness evaluation and mechanism elucidation.

Anaerobic digestion (AD) is a prevalent waste activated sludge (WAS) treatment, and optimizing methane production is a core focus of AD. Two DESs were developed in this study and significantly increased methane production, including choline chloride-urea (ChCl-Urea) 390% and chloride-ethylene glycol (ChCl-EG) 540%. Results showed that ChCl-Urea mainly disrupted extracellular polymeric substances (EPS) structures, aiding in initial sludge solubilization during pretreatment. ChCl-EG, instead, induced sludge self-driven organic solubilization and enhanced hydrolysis and acidification processes during AD process. Based on the extent to which the two DESs promoted AD for methane production, the AD process can be divided into stage Ⅰ and stage Ⅱ. In stage Ⅰ, ChCl-EG promoted methanogenesis more significantly, microbiological analysis showed both DESs enriched aceticlastic methanogens-Methanosarcina. Notably, ChCl-Urea particularly influenced polysaccharide-related metabolism, whereas ChCl-EG targeted protein-related metabolism. In stage Ⅱ, ChCl-Urea was more dominant than ChCl-EG, ChCl-Urea bolstered metabolism and ChCl-EG promoted genetic information processing in this stage. In essence, this study investigated the microbial mechanism of DES-enhanced sludge methanogenesis and provided a reference for future research.

Enhancing bioavailable carbon sources and minimizing ammonia emissions in distillery sludge and distiller's grains waste co-composting through deep eutectic solvent addition.

This study introduced two deep eutectic solvents, ChCl/oxalic acid (CO) and ChCl/ethylene glycol (CE), into a 34-day co-composting process of distillery sludge and distiller's grains waste to address challenges related to NH3 emissions. The addition of DES increased dissolved organic carbon by 68% to 92%, offering more utilizable carbon for microorganisms. SYTO9/PI staining and enzyme activity tests showed the CE group had higher bacterial activity and metabolic levels during the thermophilic phase than the control. Bacterial community analysis revealed that early dominance of Lactobacillus and Lysinibacillus in CE accelerated the onset of the thermophilic phase, reduced pile pH, and significantly decreased urease production by reducing Ureibacillus. Consequently, CE treatment substantially dropped NH3 emissions by 73% and nitrogen loss by 54%. Besides, CE fostered a more abundant functional microbial community during the cooling and maturation phases, enhancing deep degradation and humification of organic matter.

Multileaf Collimator Modeling and Commissioning for Complex Radiation Treatment Plans Using 2-Dimensional (2D) Diode Array MapCHECK2.

Purpose: This study aims to develop a data-collecting package ExpressMLC and investigate the applicability of MapCHECK2 for multileaf collimator (MLC) modeling and commissioning for complex radiation treatment plans. Materials and methods: The MLC model incorporates realistic parameters to account for sophisticated MLC features. A set of 8 single-beam plans, denoted by ExpressMLC, is created for the determination of parameters. For the commissioning of the MLC model, 4 intensity modulated radiation therapy (IMRT) plans specified by the AAPM TG 119 report were transferred to a computed tomography study of MapCHECK2, recalculated, and compared to measurements on a Varian accelerator. Both per-beam and composite-beam dose verification were conducted. Results: Through sufficient characterization of the MLC model, under 3%/2 mm and 2%/2 mm criteria, MapCHECK2 can be used to accurately verify per beam dose with gamma passing rate better than 90.9% and 89.3%, respectively, while the Gafchromic EBT3 films can achieve gamma passing rate better than 89.3% and 85.7%, respectively. Under the same criteria, MapCHECK2 can achieve composite beam dose verification with a gamma passing rate better than 95.9% and 90.3%, while the Gafchromic EBT3 films can achieve a gamma passing rate better than 96.1% and 91.8%; the p-value from the Mann Whitney test between gamma passing rates of the per beam dose verification using full MapCHECK2 package calibrated MLC model and film calibrated MLC model is .44 and .47, respectively; the p-value between those of the true composite beam dose verification is .62 and .36, respectively. Conclusion: It is confirmed that the 2-dimensional (2D) diode array MapCHECK2 can be used for data collection for MLC modeling with the combination of the ExpressMLC package of plans, whose doses are sufficient for the determination of MLC parameters. It could be a fitting alternative to films to boost the efficiency of MLC modeling and commissioning without sacrificing accuracy.

Physical and psychological correlates of somatic symptom in patients with functional constipation: a cross-sectional study.

BACKGROUND: The symptoms of functional constipation (FC) were obviously affected by mental symptoms, which was consistent with somatic symptoms. However, the characteristics of FC patients with somatic symptom remains unexplored. METHODS: Clinical characteristics including somatic symptom (SOM, PHQ-15), depression (PHQ-9), anxiety (GAD-7), quality of life (PAC-QOL), constipation (KESS), demographic variables, anatomical abnormalities and symptoms were investigated. Subsequent analyses encompassed the comparison of clinical parameters between patients with SOM + group (PHQ-15 ≥ 10) and SOM- group (PHQ-15 < 10), subgroup analysis, correlation analysis, and logistic regression. Lastly, we evaluated the somatic symptom severity (SSS) among FC patients subjected to various stressors. RESULTS: Notable disparities were observed between SOM + and SOM- groups in variety of physiological and psychological variables, including gender, stressful events, sleep disorders, reduced interest, GAD-7, PHQ-15, PHQ-9, PAC-QOL, anterior rectocele, KESS, and internal anal sphincter achalasia (IASA) (P < 0.05). Subgroup analysis affirmed consistent findings across mental symptoms. Correlation analyses revealed significant associations between SSS and KESS, anterior rectocele, GAD-7, PHQ-9, and PAC-QOL (P < 0.05). Logistic regression identified PHQ-9 (OR = 7.02, CI: 2.06-27.7, P = 0.003), GAD-7 (OR = 7.18, CI: 2.00-30.7, P = 0.004), and KESS (OR = 16.8, CI: 3.09-113, P = 0.002) as independent predictors of SSS. Elevated SSS scores were significantly associated with couple, parental, and work-related stressors (P < 0.05). CONCLUSION: A marked heterogeneity was observed between SOM + and SOM- patients of FC, with SOM + accompanied by more severe constipation, anxiety and depression symptoms. This finding underscores the importance of considering somatic symptoms in diagnosis and treatment of FC.

[Risk factors of perioperative hypertension in dental implant surgeries with bone augmentation].

OBJECTIVE: To investigate the characteristics and risk factors of perioperative hypertension during dental implant surgeries with bone augmentation. METHODS: A retrospective cohort study was conducted. Seven hundred and twenty-eight cases underwent dental implant placement and bone augmentation in Peking University School and Hospital of Stomatology from September 2021 to August 2022 were recruited in this study according to the inclusion and exclusion criteria. They were divided into different groups according to the exposure factors which were gender, age, surgical time, and surgical approach. The correlation between perioperative hypertension and the exposure factors was analyzed. RESULTS: The average systolic blood pressure variability was 9.93%±6.63% (maximum 50.41%), the average diastolic blood pressure variability was 12.45%±8.79% (maximum 68.75%), and the average mean arterial pressure variability was 10.02%±6.61% (maximum 49.48%). The incidence rate of perioperative hypertension was 26.77%. Male, age ≥ 60 years, and surgical time > 60 minutes were risk factors for perioperative hypertension (P < 0.05), and the relative risks (95%CI) were 1.74 (1.21-2.50), 2.35 (1.54-3.58), and 1.65 (1.15-2.38), respectively. There was no significant difference in the incidence of perioperative hypertension among the guided bone regeneration, sinus floor elevation with transalveolar approach, and sinus floor elevation with lateral window approach (P>0.05). However, the risk factors varied according to bone augmentation approaches. For the patients underwent guided bone rege-neration, the risk factors for perioperative hypertension included male, age ≥ 60 years, and surgical time > 60 minutes (P < 0.05). For the patients underwent maxillary sinus lift with transalveolar approach, the risk factor for perioperative hypertension was age ≥60 years (P < 0.05). For the patients underwent maxillary sinus lift with lateral window approach, male, age ≥60 years, and surgical time >60 minutes were not risk factors for perioperative hypertension (P>0.05). CONCLUSION: There was a certain risk of perioperative hypertension in oral implantation with bone augmentation. The influence of male, age ≥60 years and surgical time > 60 minutes on perioperative hypertension was related to the approach of bone augmentation.

Removal of low concentration of perchlorate from natural water by quaternized chitosan sphere (CGQS): Efficiency and mechanism research.

In this study, an innovative approach utilizing betaine as a raw material was employed to effectively modify the surface of chitosan with quaternary ammonium groups. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectrometer (FTIR) characterization showed that the quaternary ammonium groups on betaine were successfully loaded on the chitosan surface. The effects of dosage, pH, initial perchlorate concentration, temperature and co-existing anions on the removal efficiency of perchlorate were investigated. The saturated adsorption capacity of CGQS was 35.41 mg/g under natural condition. The impact of initial perchlorate concentrations and column flow rates on the column adsorption experiments were investigated, as well as natural water tests. Sterilizing performance experiments of CGQS were carried out innovatively. Under the condition of initial concentration of 0.5 mg/L, 9 BV/h (bed volume per hour), the effluent natural water was up to standard (≤0.07 mg/L) with a treatment capacity of 210 BV/g, and the sterilizing rate of CGQS was up to 97.02%. The proposed adsorption mechanisms involved surface pore adsorption, electrostatic adsorption of quaternary ammonium groups, and ion exchange between chloride and perchlorate ions. The CGQS prepared in this work had great potential for treating trace perchlorate contamination in natural water.

Fractal Analysis of Left Ventricular Trabeculae in Patients with End-Stage Renal Disease: A Random Survival Tree Analysis.

BACKGROUND: The complexity of left ventricular (LV) trabeculae is related to the prognosis of several cardiovascular diseases. PURPOSE: To evaluate the prognostic value of LV trabecular complexity in patients with end-stage renal disease (ESRD). STUDY TYPE: Prospective outcome study. POPULATION: 207 participants on maintenance dialysis, divided into development (160 patients from 2 centers) and external validation (47 patients from a third center) cohorts, and 72 healthy controls. FIELD STRENGTH: 3.0T, steady-state free precession (SSFP) and modified Look-Locker imaging sequences. ASSESSMENT: All participants had their trabecular complexity quantified by fractal analysis using cine SSFP images. Patients were followed up every 2 weeks until April 2023, or endpoint events happened. Random Forest (RF) and Cox regression models including age, diabetes, LV mass index, mean basal fractal dimension (FD), and left atrial volume index, were developed to predict major adverse cardiac events (MACE). Patients were divided into low- and high-risk groups based on scores derived from the RF model and survival compared. STATISTICAL TESTS: Receiver operating characteristic curve analysis; Kaplan-Meier survival analysis with log rank tests; Harrel's C-index to assess model performance. A P value <0.05 was considered statistically significant. RESULTS: Fifty-five patients (26.57%) experienced MACE during a median follow-up time of 21.83 months. An increased mean basal FD (≥1.324) was associated with a significantly higher risk of MACE. The RF model (C-index: 0.81) had significantly better discrimination than the Cox regression model (C-index: 0.74). Participants of the external validation dataset classified into the high-risk group had a hazard of experiencing MACE increased by 12.29 times compared to those in the low-risk group. DATA CONCLUSION: LV basal FD was an independent predictor for MACE in patients with ESRD. Reliable risk stratification models could be generated based on LV basal FD and other MRI variables using RF analysis. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Efficacy of postoperative analgesia with intravenous paracetamol and mannitol injection, combined with thoracic paravertebral nerve block in post video-assisted thoracoscopic surgery pain: a prospective, randomized, double-blind controlled trial.

BACKGROUND: Although video-assisted thoracoscopic surgery (VATS) has advantages of reduced injury and faster healing, patients still endure moderate and severe postoperative pain. Paracetamol and mannitol injection, the first acetaminophen injection in China, has the advantages of convenient administration, rapid onset of action, and no first-pass effect. This aim of this study was to investigate the efficacy of postoperative analgesia with paracetamol and mannitol injection, combined with thoracic paravertebral nerve block (TPVB) in post VATS pain. METHODS: This study was a single-center, prospective, randomized, double-blind controlled clinical trial. Patients scheduled for VATS were randomly divided into three groups, general anesthesia group (Group C), TPVB group (Group T) and TPVB + paracetamol and mannitol injection group (Group TP). In this study, the primary outcome was determined as visual analog scale (VAS) scores at rest and coughing, the secondary observation outcomes were the first time to use analgesic pump, the total consumption of oxycodone in the analgesic pump, number of effective and total analgesic pump compressions at first 48 h postoperatively, the perioperative consumption of sufentanil, time to extubation, hospital length of stay, urine volume, and the incidence of adverse events. RESULTS: In a state of rest and cough, patients in the Group TP showed significantly lower VAS pain scores at 1, 12, 24, and 48 postoperative-hour compared with Group C and Group T. Intraoperative sufentanil and postoperative oxycodone consumption, the first time to press analgesic pump, the times of effective and total compressions of patient- controlled analgesia (PCA) were lower than those of the Group C and Group T. Interestingly, urine output was higher in Group TP. There were no differences between the three groups in terms of extubation time, length of hospital stay and adverse effects, indicating that intravenous paracetamol and mannitol injection is an effective and safe perioperative analgesia method. CONCLUSIONS: Paracetamol and mannitol injection, combined with TPVB may provide important beneficial effects on acute pain control and reduce the consumption of opioid in patients undergoing VATS. TRIAL REGISTRATION: The trial was registered on Jun 19, 2023 in the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=199315 ), registration number ChiCTR2300072623 (19/06/2023).

Engineering the d-Orbital Energy of Metal-Organic Frameworks-Based Solid-State Electrolytes for Lithium-Metal Batteries.

Having an orbital-level understanding of the relationship between the electronic state of a central metal in metal-organic frameworks (MOFs) as solid-state electrolytes (SSEs) and Li+ ion conductivity is crucial yet challenging for lithium-metal batteries (LMBs). In this study, we report the synthesis of functionalized UiO-66 as a model system to investigate the relationship between the d-band energy of Zr 3d orbitals and Li+ ion conductivity. Specifically, the NO2 group in electron-withdrawing NO2-decorated UiO-66 (NO2-UiO-66) can capture electron from ZrO8 sites, resulting the increased energy in 3dz2 and 3dxz/yz orbitals of Zr atom. The high-energy 3dz2 and 3dxz/yz orbitals of Zr in NO2-UiO-66 hybridize with the 2pz and 2px/y orbitals of O in ClO4-, leading to decreased antibonding orbital energy and resulting in a strong adsorption, ultimately immobilizing the anions and enhancing ion conductivities. Establishing the correlation between the d-orbital energy and Li+ ion conductivity may create a descriptor for designing efficient SSEs for LMBs.

Enhanced meningeal lymphatic drainage ameliorates lipopolysaccharide-induced brain injury in aged mice.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is an acute cerebral dysfunction caused by sepsis. Neuroinflammation induced by sepsis is considered a potential mechanism of SAE; however, very little is known about the role of the meningeal lymphatic system in SAE. METHODS: Sepsis was established in male C57BL/6J mice by intraperitoneal injection of 5 mg/kg lipopolysaccharide, and the function of meningeal lymphatic drainage was assessed. Adeno-associated virus 1-vascular endothelial growth factor C (AAV1-VEGF-C) was injected into the cisterna magna to induce meningeal lymphangiogenesis. Ligation of deep cervical lymph nodes (dCLNs) was performed to induce pre-existing meningeal lymphatic dysfunction. Cognitive function was evaluated by a fear conditioning test, and inflammatory factors were detected by enzyme-linked immunosorbent assay. RESULTS: The aged mice with SAE showed a significant decrease in the drainage of OVA-647 into the dCLNs and the coverage of the Lyve-1 in the meningeal lymphatic, indicating that sepsis impaired meningeal lymphatic drainage and morphology. The meningeal lymphatic function of aged mice was more vulnerable to sepsis in comparison to young mice. Sepsis also decreased the protein levels of caspase-3 and PSD95, which was accompanied by reductions in the activity of hippocampal neurons. Microglia were significantly activated in the hippocampus of SAE mice, which was accompanied by an increase in neuroinflammation, as indicated by increases in interleukin-1 beta, interleukin-6 and Iba1 expression. Cognitive function was impaired in aged mice with SAE. However, the injection of AAV1-VEGF-C significantly increased coverage in the lymphatic system and tracer dye uptake in dCLNs, suggesting that AAV1-VEGF-C promotes meningeal lymphangiogenesis and drainage. Furthermore, AAV1-VEGF-C reduced microglial activation and neuroinflammation and improved cognitive dysfunction. Improvement of meningeal lymphatics also reduced sepsis-induced expression of disease-associated genes in aged mice. Pre-existing lymphatic dysfunction by ligating bilateral dCLNs aggravated sepsis-induced neuroinflammation and cognitive impairment. CONCLUSION: The meningeal lymphatic drainage is damaged in sepsis, and pre-existing defects in this drainage system exacerbate SAE-induced neuroinflammation and cognitive dysfunction. Promoting meningeal lymphatic drainage improves SAE. Manipulation of meningeal lymphangiogenesis could be a new strategy for the treatment of SAE.