Co-mutation of OsLPR1/3/4/5 provides a promising strategy to minimize Cd contamination in rice grains.

Minimizing cadmium (Cd) contamination in rice grains is crucial for ensuring food security and promoting sustainable agriculture. Utilizing genetic modification to generate rice varieties with low Cd accumulation is a promising strategy due to its cost-effectiveness and operational simplicity. Our study demonstrated that the CRISPR-Cas9-mediated quadruple mutation of the multicopper oxidase genes OsLPR1/3/4/5 in the japonica rice cultivar Tongjing 981 had little effect on yields. However, a notable increase was observed in the cell wall functional groups that bind with Cd. As a result, the quadruple mutation of OsLPR1/3/4/5 enhanced Cd sequestration within the cell wall while reducing Cd concentrations in both xylem and phloem sap, thereby inhibiting Cd transport from roots to shoots. Consequently, Cd concentrations in brown rice and husk in oslpr1/3/4/5 quadruple mutants (qm) decreased by 52% and 55%, respectively, compared to the wild-type. These findings illustrate that the quadruple mutation of OsLPR1/3/4/5 is an effective method for minimizing Cd contamination in rice grains without compromising yields. Therefore, the quadruple mutation of OsLPR1/3/4/5 via biotechnological pathways may represent a valuable strategy for the generation of new rice varieties with low Cd accumulation.

Effect of tubastatin A on NLRP3 inflammasome activation in macrophages under hypoxia/reoxygenation conditions.

BACKGROUND: There are currently no effective drugs to mitigate the ischemia/reperfusion injury caused by fluid resuscitation after hemorrhagic shock (HS). The aim of this study was to explore the potential of the histone deacetylase 6 (HDAC6)-specific inhibitor tubastatin A (TubA) to suppress nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation in macrophages under hypoxia/reoxygenation (H/R) conditions. METHODS: The viability of RAW264.7 cells subjected to H/R after treatment with different concentrations of TubA was assessed using a cell-counting kit-8 (CCK8) assay. Briefly, 2.5 µmol/L TubA was used with RAW264.7 cells under H/R condition. RAW264.7 cells were divided into three groups, namely the control, H/R, and TubA groups. The levels of reactive oxygen species (ROS) in the cells were detected using fluorescence microscopy. The protein expression of HDAC6, heat shock protein 90 (Hsp90), inducible nitric oxide synthase (iNOS), NLRP3, gasdermin-D (GSDMD), Caspase-1, GSDMD-N, and Caspase-1 p20 was detected by western blotting. The levels of interleukin-1ß (IL-1ß) and IL-18 in the supernatants were detected using enzyme-linked immunosorbent assay (ELISA). RESULTS: HDAC6, Hsp90, and iNOS expression levels were significantly higher (P<0.01) in the H/R group than in the control group, but lower in the TubA group than in the H/R group (P<0.05). When comparing the H/R group to the control group, ROS levels were significantly higher (P<0.01), but significantly reduced in the TubA group (P<0.05). The H/R group had higher NLRP3, GSDMD, Caspase-1, GSDMD-N, and Caspase-1 p20 expression levels than the control group (P<0.05), however, the TubA group had significantly lower expression levels than the H/R group (P<0.05). IL-1ß and IL-18 levels in the supernatants were significantly higher in the H/R group compared to the control group (P<0.01), but significantly lower in the TubA group compared to the H/R group (P<0.01). CONCLUSION: TubA inhibited the expression of HDAC6, Hsp90, and iNOS in macrophages subjected to H/R. This inhibition led to a decrease in the content of ROS in cells, which subsequently inhibited the activation of the NLRP3 inflammasome and the secretion of IL-1ß and IL-18.

Molecular characterization and clinical relevance of metabolic signature subtypes in gastric cancer.

Metabolic reprogramming dictates tumor molecular attributes and therapeutic potentials. However, the comprehensive metabolic characteristics in gastric cancer (GC) remain obscure. Here, metabolic signature-based clustering analysis identifies three subtypes with distinct molecular and clinical features: MSC1 showed better prognosis and upregulation of the tricarboxylic acid (TCA) cycle and lipid metabolism, combined with frequent TP53 and RHOA mutation; MSC2 had moderate prognosis and elevated nucleotide and amino acid metabolism, enriched by intestinal histology and mismatch repair deficient (dMMR); and MSC3 exhibited poor prognosis and enhanced glycan and energy metabolism, accompanied by diffuse histology and frequent CDH1 mutation. The Shandong Provincial Hospital (SDPH) in-house dataset with matched transcriptomic, metabolomic, and spatial-metabolomic analysis also validated these findings. Further, we constructed the metabolic subtype-related prognosis gene (MSPG) scoring model to quantify the activity of individual tumors and found a positive correlation with cuproptosis signaling. In conclusion, comprehensive recognition of the metabolite signature can enhance the understanding of diversity and heterogeneity in GC.

Clinical features and molecular landscape of cuproptosis signature-related molecular subtype in gastric cancer.

Recent studies have highlighted the biological significance of cuproptosis in disease occurrence and development. However, it remains unclear whether cuproptosis signaling also has potential impacts on tumor initiation and prognosis of gastric cancer (GC). In this study, 16 cuproptosis-related genes (CRGs) transcriptional profiles were harnessed to perform the regularized latent variable model-based clustering in GC. A cuproptosis signature risk scoring (CSRS) scheme, based on a weighted sum of principle components of the CRGs, was used to evaluate the prognosis and risk of individual tumors of GC. Four distinct cuproptosis signature-based clusters, characterized by differential expression patterns of CRGs, were identified among 1136 GC samples across three independent databases. The four clusters were also associated with different clinical outcomes and tumor immune contexture. Based on the CSRS, GC patients can be divided into CSRS-High and CSRS-Low subtypes. We found that DBT, MTF1, and ATP7A were significantly elevated in the CSRS-High subtype, while SLC31A1, GCSH, LIAS, DLAT, FDX1, DLD, and PDHA1 were increased in the CSRS-Low subtype. Patients with CSRS-Low score were characterized by prolonged survival time. Further analysis indicated that CSRS-Low score also correlated with greater tumor mutation burden (TMB) and higher mutation rates of significantly mutated genes (SMG) in GC. In addition, the CSRS-High subtype harbored more significantly amplified focal regions related to tumorigenesis (3q27.1, 12p12.1, 11q13.3, etc.) than the CSRS-Low tumors. Drug sensitivity analyses revealed the potential compounds for the treatment of gastric cancer with CSRS-High score, which were experimentally validated using GC cells. This study highlights that cuproptosis signature-based subtyping is significantly associated with different clinical features and molecular landscape of GC. Quantitative evaluation of the CSRS of individual tumors will strengthen our understanding of the occurrence and development of cuproptosis and the treatment progress of GC.

The role and therapeutic potential of SIRTs in sepsis.

Sepsis is a life-threatening organ dysfunction caused by the host's dysfunctional response to infection. Abnormal activation of the immune system and disturbance of energy metabolism play a key role in the development of sepsis. In recent years, the Sirtuins (SIRTs) family has been found to play an important role in the pathogenesis of sepsis. SIRTs, as a class of histone deacetylases (HDACs), are widely involved in cellular inflammation regulation, energy metabolism and oxidative stress. The effects of SIRTs on immune cells are mainly reflected in the regulation of inflammatory pathways. This regulation helps balance the inflammatory response and may lessen cell damage and organ dysfunction in sepsis. In terms of energy metabolism, SIRTs can play a role in immunophenotypic transformation by regulating cell metabolism, improve mitochondrial function, increase energy production, and maintain cell energy balance. SIRTs also regulate the production of reactive oxygen species (ROS), protecting cells from oxidative stress damage by activating antioxidant defense pathways and maintaining a balance between oxidants and reducing agents. Current studies have shown that several potential drugs, such as Resveratrol and melatonin, can enhance the activity of SIRT. It can help to reduce inflammatory response, improve energy metabolism and reduce oxidative stress, showing potential clinical application prospects for the treatment of sepsis. This review focuses on the regulation of SIRT on inflammatory response, energy metabolism and oxidative stress of immune cells, as well as its important influence on multiple organ dysfunction in sepsis, and discusses and summarizes the effects of related drugs and compounds on reducing multiple organ damage in sepsis through the pathway involving SIRTs. SIRTs may become a new target for the treatment of sepsis and its resulting organ dysfunction, providing new ideas and possibilities for the treatment of this life-threatening disease.

The role of upfront lenalidomide maintenance for primary central nervous system lymphoma following first-line methotrexate treatment: A retrospective study.

BACKGROUND: Consolidation therapy improves the duration of response among patients with primary central nervous system lymphoma (PCNSL). Lenalidomide maintenance has shown encouraging results in older patients with PCNSL. Herein, we performed a retrospective, single-center analysis to evaluate the effect of lenalidomide maintenance on the duration of response in patients with newly-diagnosed PCNSL. METHODS: Sixty-nine adult patients with PCNSL who achieved complete remission or partial remission (PR) after induction therapy were enrolled. The median age of patients was 58.0 years. The maintenance group (n = 35) received oral lenalidomide (25 mg/day) for 21 days, every 28 days for 24 months; the observation group did not undergo any further treatment. RESULTS: After a median follow-up of 32.6 months, the maintenance group experienced fewer relapse events. However, the median progression-free survival (PFS) was similar between groups (36.1 vs. 30.6 months; hazard ratio, 0.78; 95% confidence interval, 0.446). Lenalidomide maintenance significantly improved PFS and overall survival (OS) only among patients who experienced PR after induction. The median duration of lenalidomide maintenance was 18 months; lenalidomide was well tolerated and minimally impacted the quality of life. CONCLUSIONS: The present study was the first to evaluate lenalidomide maintenance as a frontline treatment among patients with PCNSL, PFS and OS did not improve, although the safety profile was satisfactory.

Genetic and molecular characterization of metabolic pathway-based clusters in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive types of squamous cell carcinoma and represents a significant proportion of esophageal cancer. Metabolic reprogramming plays a key role in the occurrence and development of ESCC. Unsupervised clustering analysis was employed to stratify ESCC samples into three clusters: MPC1-lipid type, MPC2-amino acid type, and MPC3-energy type, based on the enrichment scores of metabolic pathways extracted from the Reactome database. The MPC3 cluster exhibited characteristics of energy metabolism, with heightened glycolysis, cofactors, and nucleotide metabolism, showing a trend toward increased aggressiveness and poorer survival rates. On the other hand, MPC1 and MPC2 primarily involved lipid and amino acid metabolism, respectively. In addition, liquid chromatography‒mass spectrometry-based metabolite profiles and potential therapeutic agents were explored and compared among ESCC cell lines with different MPCs. MPC3 amplified energy metabolism markers, especially carnitines. In contrast, MPC1 and MPC2 predominantly had elevated levels of lipids (primarily triacylglycerol) and amino acids, respectively. Furthermore, MPC3 demonstrated a suboptimal clinical response to PD-L1 immunotherapy but showed increased sensitivity to the doramapimod chemotherapy regimen, as evident from drug sensitivity evaluations. These insights pave the way for a more personalized therapeutic approach, potentially enhancing treatment precision for ESCC patients.

Excessive iron deposition in root apoplast is involved in growth arrest of roots in response to low pH.

The rhizotoxicity of protons (H+) in acidic soils is a fundamental constraint that results in serious yield losses. However, the mechanisms underlying H+-mediated inhibition of root growth are poorly understood. In this study, we revealed that H+-induced root growth inhibition in Arabidopsis depends considerably on excessive iron deposition in the root apoplast. Reducing such aberrant iron deposition by decreasing the iron supply or disrupting the ferroxidases LOW PHOSPHATE ROOT 1 (LPR) and LPR2 attenuates the inhibitory effect of H+ on primary root growth efficiently. Further analysis showed that excessive iron deposition triggers a burst of highly reactive oxygen species, consequently impairing normal root development. Our study uncovered a valuable strategy for improving the ability of plants to tolerate H+ toxicity by manipulating iron availability.

Research progress of exosomes in the angiogenesis of digestive system tumour.

Malignant tumours of the digestive system cover a wide range of diseases that affect the health of people to a large extent. Angiogenesis is indispensable in the development, and metastasis of tumours, mainly in two ways: occupation or formation. Vessels can provide nutrients, oxygen, and growth factors for tumours to encourage growth and metastasis, so cancer progression depends on simultaneous angiogenesis. Recently, exosomes have been proven to participate in the angiogenesis of tumours. They influence angiogenesis by binding to tyrosine kinase receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 with different affinities, regulating Yap-VEGF pathway, Akt pathway or other signaling pathway. Additionally, exosomes are potential therapeutic vectors that can deliver many types of cargoes to different cells. In this review, we summarize the roles of exosomes in the angiogenesis of digestive system tumours and highlight the clinical application prospects, directly used as targers or delivery vehicles, in antiangiogenic therapy.

Efficacy and safety of narrowband ultraviolet B versus combined ultraviolet A/narrowband ultraviolet B phototherapy in the treatment of chronic atopic dermatitis: A randomised double-blind study.

Phototherapy is a useful treatment modality for atopic dermatitis (AD). This is a prospective randomised double-blind study comparing the clinical efficacy of combined ultraviolet-A (UVA)/narrowband ultraviolet-B (NBUVB) versus NBUVB phototherapy in the treatment of chronic AD. Patients with moderate-to-severe AD were randomised to receive either UVA/NBUVB or NBUVB phototherapy twice weekly over 12 weeks. At baseline, weeks 6 and 12, Eczema Area And Severity Index (EASI), itch score and adverse effects were assessed. At baseline and week 12, disease-related quality of life was evaluated using the Dermatology Life Quality Index (DLQI). Nine patients were randomised to receive UVA/NBUVB and 10 received NBUVB. At week 12, both groups showed significant improvement in EASI and itch scores (p < 0.05). Significant improvement in DLQI was seen in the UVA/NBUVB arm (p = 0.009) with a trend towards improvement in the NBUVB arm (p = 0.11). The efficacy of both modalities were comparable, as were reported adverse effects aside from skin dryness which was higher in the NBUVB arm (40% vs. 0%, p = 0.033). Combined UVA/NBUVB and NBUVB phototherapy have comparable clinical efficacy and safety in the treatment of chronic AD. NBUVB may induce greater skin dryness.

Phospholysine phosphohistidine inorganic pyrophosphate phosphatase suppresses insulin-like growth factor 1 receptor expression to inhibit cell adhesion and proliferation in gastric cancer.

Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has recently emerged as a novel tumor suppressor. Researchers have observed that LHPP plays a crucial role in inhibiting proliferation, growth, migration, invasion, and cell metabolism across various cancers. Nevertheless, the specific functions and underlying mechanisms of LHPP as a tumor suppressor in gastric cancer (GC) require further exploration. The expression of LHPP was assessed in human GC specimens and cell lines. Various assays were employed to evaluate the impact of LHPP on GC cells. RNA sequencing and Gene Set Enrichment Analysis were conducted to unravel the mechanism through which LHPP regulates GC cell behavior. Additionally, xenograft nude mouse models were utilized to investigate the in vivo effects of LHPP. The findings indicate that LHPP, functioning as a tumor suppressor, is downregulated in both GC tissues and cells. LHPP emerges as an independent risk factor for GC patients, and its expression level exhibits a positive correlation with patient prognosis. LHPP exerts inhibitory effects on the adhesion and proliferation of GC cells by suppressing the expression of insulin-like growth factor 1 receptor (IGF1R) and modulating downstream signaling pathways. Consequently, LHPP holds potential as a biomarker for targeted therapy involving IGF1R inhibition in GC patients.

A multicenter prospective randomized controlled trial investigating the effects of combustion-free nicotine alternatives on cardiovascular risk factors and metabolic parameters in individuals with type 2 diabetes who smoke: the DiaSmokeFree study protocol.

Stopping smoking is crucial for public health and especially for individuals with diabetes. Combustion-free nicotine alternatives like e-cigarettes and heated tobacco products are increasingly being used as substitutes for conventional cigarettes, contributing to the decline in smoking prevalence. However, there is limited information about the long-term health impact of those products in patients with diabetes. This randomized controlled trial aims to investigate whether switching from conventional cigarettes to combustion-free nicotine alternatives will lead to a measurable improvement in cardiovascular risk factors and metabolic parameters over a period of 2 years in smokers with type 2 diabetes. The multicenter study will be conducted in seven sites across four countries. A total of 576 smokers with type 2 diabetes will be randomly assigned (1:2 ratio) to either standard of care with brief cessation advice (Control Arm) or combustion-free nicotine alternatives use (Intervention Arm). The primary end point is the change in the proportion of patients with metabolic syndrome between baseline and the 2-year follow-up. Additionally, the study will analyze the absolute change in the sum of the individual factors of metabolic syndrome at each study time point. Patient recruitment has started in September 2021 and enrollment is expected to be completed by December 2023. Results will be reported in 2026. This study may provide valuable insights into cardiovascular and metabolic health benefits or risks associated with using combustion-free nicotine alternatives for individuals with type 2 diabetes who are seeking alternatives to tobacco cigarette smoking. The study protocol, informed consent forms, and relevant documents were approved by seven ethical review boards. Study results will be disseminated through articles published in high-quality, peer-reviewed journals and presentations at conferences.

Fragment databases from screened ligands for drug discovery (FDSL-DD).

Fragment-based drug design (FBDD) is one major drug discovery method employed in computer-aided drug discovery. Due to its inherent limitations, this process experiences long processing times and limited success rates. Here we present a new Fragment Databases from Screened Ligands Drug Design method (FDSL-DD) that intelligently incorporates information about fragment characteristics into a fragment-based design approach to the drug development process. The initial step of the FDSL-DD is the creation of a fragment database from a library of docked, drug-like ligands for a specific target, which deviates from the traditional in silico FBDD strategy, incorporating structure-based design screening techniques to combine the advantages of both approaches. Three different protein targets have been tested in this study to demonstrate the potential of the created fragment library and FDSL-DD. Utilizing the FDSL-DD led to an increase in binding affinity for each protein target. The most substantial increase was exhibited by the ligand designed for TIPE2, with a 3.6 kcalmol-1 difference between the top ligand from the FDSL-DD and top ligand from the high throughput virtual screening (HTVS). Using drug-like ligands in the initial HTVS allows for a greater search of chemical space, with higher efficiency in fragments selection, less grid boxes, and potentially identifying more interactions.

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OBJECTIVES: Based on peripheral blood lymphocyte subsets and common laboratory test indexes, this study aimed to construct a predictive scoring system for intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD). METHODS: Children hospitalized in Tianjin Children's Hospital from January 2021 to March 2023 were included in the study (185 cases of IVIG-sensitive KD and 41 cases of IVIG -resistant KD). Forty-six healthy children matched for age and gender were selected as controls. The relative percentage and absolute counts of peripheral lymphocyte subsets were measured by flow cytometry. Multivariate logistic regression was used to identify the predictive factors for IVIG-resistant KD and to construct a predictive scoring system for predicting IVIG-resistant KD. RESULTS: The multivariate logistic regression analysis showed that CD4+ T cell absolute count, natural killer cell absolute count, serum sodium level, globulin level, and total bilirubin level were identified as predictive factors for IVIG-resistant KD (P<0.05). The predictive scoring system based on these factors achieved a sensitivity of 70.7% and a specificity of 83.8% in predicting IVIG-resistant KD. CONCLUSIONS: Peripheral blood lymphocyte subsets can serve as predictive indicators for IVIG-resistant KD in children. The introduction of this indicator and the establishment of a scoring system based on it can provide a higher accuracy in predicting IVIG-resistant KD in children.

Self-activated superhydrophilic green ZnIn2S4 realizing solar-driven overall water splitting: close-to-unity stability for a full daytime.

Engineering an efficient semiconductor to sustainably produce green hydrogen via solar-driven water splitting is one of the cutting-edge strategies for carbon-neutral energy ecosystem. Herein, a superhydrophilic green hollow ZnIn2S4 (gZIS) was fabricated to realize unassisted photocatalytic overall water splitting. The hollow hierarchical framework benefits exposure of intrinsically active facets and activates inert basal planes. The superhydrophilic nature of gZIS promotes intense surface water molecule interactions. The presence of vacancies within gZIS facilitates photon energy utilization and charge transfer. Systematic theoretical computations signify the defect-induced charge redistribution of gZIS enhancing water activation and reducing surface kinetic barriers. Ultimately, the gZIS could drive photocatalytic pure water splitting by retaining close-to-unity stability for a full daytime reaction with performance comparable to other complex sulfide-based materials. This work reports a self-activated, single-component cocatalyst-free gZIS with great exploration value, potentially providing a state-of-the-art design and innovative aperture for efficient solar-driven hydrogen production to achieve carbon-neutrality.

Antioxidant activities, phenolic compounds, and mineral composition of seed from Acacia retinodes, A. Provincialis and A. Tenuissima.

Seeds of the species Acacia retinodes, A. provincialis, and A. tenuissima) from different growing locations were analysed for their mineral composition, free and bound polyphenols, and flavonoids. Previous research has studied these compounds in only a limited number of Acacia species, and only one study reports significant differences between three species. All species were rich in potassium (353 - 427 mg/100 g), sodium (14 - 240 mg/100 g) and iron (7 - 8 mg/100 g). The free polyphenol extracts of all species had higher total phenolic content, total flavonoid content and antioxidant activities than their bound counterparts, indicating the possibility of higher bioavailability than the bound polyphenol extracts. The predominant phenolic compounds found in the Acacia polyphenol seed extracts were 6-Hydroxy-2-methylindole and 2,2'-Methylenebis(6-tert-butyl-methylphenol), though no phenolic compounds were identified in the bound extracts of A. retinodes Grampians and A. provincialis Tarrington. Other compounds identified in the seed extracts include sucrose, d-fructofuranose and d-pinitol.

Identification of a ferroptosis-related gene signature predicting recurrence in stage II/III colorectal cancer based on machine learning algorithms.

Background: Colorectal cancer (CRC) is one of the most prevalent cancer types globally. A survival paradox exists due to the inherent heterogeneity in stage II/III CRC tumor biology. Ferroptosis is closely related to the progression of tumors, and ferroptosis-related genes can be used as a novel biomarker in predicting cancer prognosis. Methods: Ferroptosis-related genes were retrieved from the FerrDb and KEGG databases. A total of 1,397 samples were enrolled in our study from nine independent datasets, four of which were integrated as the training dataset to train and construct the model, and validated in the remaining datasets. We developed a machine learning framework with 83 combinations of 10 algorithms based on 10-fold cross-validation (CV) or bootstrap resampling algorithm to identify the most robust and stable model. C-indice and ROC analysis were performed to gauge its predictive accuracy and discrimination capabilities. Survival analysis was conducted followed by univariate and multivariate Cox regression analyses to evaluate the performance of identified signature. Results: The ferroptosis-related gene (FRG) signature was identified by the combination of Lasso and plsRcox and composed of 23 genes. The FRG signature presented better performance than common clinicopathological features (e.g., age and stage), molecular characteristics (e.g., BRAF mutation and microsatellite instability) and several published signatures in predicting the prognosis of the CRC. The signature was further stratified into a high-risk group and low-risk subgroup, where a high FRG signature indicated poor prognosis among all collected datasets. Sensitivity analysis showed the FRG signature remained a significant prognostic factor. Finally, we have developed a nomogram and a decision tree to enhance prognosis evaluation. Conclusion: The FRG signature enabled the accurate selection of high-risk stage II/III CRC population and helped optimize precision treatment to improve their clinical outcomes.

Risk factors of Omicron variant associated acute encephalitis/encephalopathy in children.

BACKGROUND: Outbreak of Omicron BA.2 in Taiwan led to an increased number of acute encephalitis/encephalopathy cases in children and several fatal cases drew public attention. In pre-Omicron period, pediatric cases of COVID-19-associated acute encephalitis have been reported and during Omicron epidemic, febrile convulsions, encephalitis were mentioned more frequently. The outcome of patients with neurological complications was worse. However, few studies investigated the risk factors, pathophysiology and prognosis of COVID-19-associated encephalitis/encephalopathy. Here, we describe the presentation of pediatric cases of COVID-19-associated acute encephalitis/encephalopathy and explore the associated risk factors. METHODS: Pediatric patients with confirmed SARS-CoV-2 infections were prospectively enrolled at admission at Chang Gung Memorial Hospital between April and August 2022. Patients were categorized into groups of acute encephalitis/encephalopathy, febrile convulsions or mild disease. Demographic descriptions, clinical manifestations and laboratory data were collected. RESULTS: Of 288 acute COVID-19 patients, there were 38 (13.2%) acute encephalitis/encephalopathy, 40 (13.9%) febrile convulsions, and 210 (72.9%) mild disease. Among acute encephalitis/encephalopathy group, the mean age was 68.3 ± 45.0 months. The common neurological symptoms were lethargy (65.8%), seizures (52.6%), and impaired consciousness (34.2%). Over 3 years old (adjusted odds ratio [aOR]: 7.57, p < 0.001), absolute neutrophil count ≥3150/µL (aOR: 5.46, p = 0.008), and procalcitonin ≥0.5 ng/mL (aOR: 4.32, p = 0.021) were independent factors for acute encephalitis/encephalopathy. CONCLUSIONS: Most cases of COVID-19-associated acute encephalitis/encephalopathy showed no evidence of direct viral invasion but associations with older age, increased peripheral neutrophil, and serum procalcitonin. These findings may imply the neutrophil-mediated systemic inflammatory response plays an important role on central nerve system, leading to cerebral dysfunction.