Enhancing the Performance of 2D Ni-Fe Layered Double Hydroxides by Cabbage-Inspired Carbon Conjunction for Oxygen Evolution Reactions.

Layered double hydroxide (LDH) nanosheets as one type of two-dimensional materials have garnered increasing attention in the field of oxygen evolution reaction (OER) in recent decades. To address the challenges associated with poor conductivity and limited electron and charge transfer capability in LDH materials, we have developed a straightforward one-pot synthesis method to successfully fabricate a composite material with a microstructure resembling cabbage, which encompasses NiFe-LDH and nanocarbon (referred as NiFe-LDH@C). Atomic force microscopy (AFM) and high-resolution transmission electron microscopy (HRTEM) revealed that the monolayer NiFe-LDH with a height of ~0.5-0.8 nm is uniformly distributed and closely bonded to the carbon support, leading to a significant enhancement in conductivity and facilitating faster electron and charge transfer. Moreover, the NiFe-LDH@C exhibits a substantial number of surface defect sites, which enhances the interaction with oxygen species. This dual enhancement in charge transfer and oxygen species-mediated transfer greatly improves the catalytic OER performance, which is further corroborated by theoretical calculations. Notably, the Ni10Fe6-LDH@C with the highest concentration of surface oxygen vacancies demonstrated superior water oxidation performance, surpassing commercially available RuO2 catalysts; an OER overpotential of 231 mV@10 mA cm-2 with a Tafel slope of 71 mV dec-1 was achieved.

Progress in the application of nanoparticles for the treatment of fungal infections: A review.

The burden of fungal infections on human health is increasing worldwide. Aspergillus, Candida, and Cryptococcus are the top three human pathogenic fungi that are responsible for over 90% of infection-related deaths. Moreover, effective antifungal therapeutics are lacking, primarily due to host toxicity, pathogen resistance, and immunodeficiency. In recent years, nanomaterials have proved not only to be more efficient antifungal therapeutic agents but also to overcome resistance against fungal medication. This review will examine the limitations of standard antifungal therapy as well as focus on the development of nanomaterials.

5-Methylcytosine transferase NSUN2 drives NRF2-mediated ferroptosis resistance in non-small cell lung cancer.

RNA 5-methylcytosine (m5C) is an abundant chemical modification in mammalian RNAs and plays crucial roles in regulating vital physiological and pathological processes, especially in cancer. However, the dysregulation of m5C and its underlying mechanisms in non-small cell lung cancer (NSCLC) remain unclear. Here we identified that NSUN2, a key RNA m5C methyltransferase, is highly expressed in NSCLC tumor tissue. We found elevated NSUN2 expression levels strongly correlate with tumor grade and size, predicting poor outcomes for NSCLC patients. Furthermore, RNA-seq and subsequent confirmation studies revealed the antioxidant-promoting transcription factor NRF2 is a target of NSUN2, and depleting NSUN2 decreases the expression of NRF2 and increases the sensitivity of NSCLC cells to ferroptosis activators both in vitro and in vivo. Intriguingly, the methylated-RIP-qPCR assay results indicated that NRF2 mRNA has a higher m5C level when NSUN2 is overexpressed in NSCLC cells but shows no significant changes in the NSUN2 methyltransferase-deficient group. Mechanistically, we confirmed that NSUN2 upregulates the expression of NRF2 by enhancing the stability of NRF2 mRNA through the m5C modification within its 5'UTR region recognized by the specific m5C reader protein YBX1, rather than influencing its translation. In subsequent rescue experiments, we show knocking down NRF2 diminished the proliferation, migration, and ferroptosis tolerance mediated by NSUN2 overexpression. In conclusion, our study unveils a novel regulatory mechanism in which NSUN2 sustains NRF2 expression through an m5C-YBX1-axis, suggesting that targeting NSUN2 and its regulated ferroptosis pathway might offer promising therapeutic strategies for NSCLC patients.

Engineered CRISPRa System for Precise and Multiplex Gene Regulation Using a Hybrid dCas12a Variant and Hairpin-Spacer crRNAs.

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a nucleases have emerged as a promising alternative to CRISPR-Cas9 in gene editing and expression regulation. However, the adoption of Cas12a has been hindered due to general off-target activities and limited efficiency. Here, we utilized a hybrid engineered Cas12a variant and hairpin-spacer crRNAs (h-CAP) to enhance the specificity and efficiency of the CRISPR-Cas12a system. Leveraging the h-CAP strategy, we demonstrate both single-base-specific and multiplex gene expression regulation in human cells.

A self-assembled graphene oxide adjuvant induces both enhanced humoral and cellular immune responses in influenza vaccine.

Antiviral vaccine is essential for preventing and controlling virus spreading, along with declining morbidity and mortality. A major challenge in effective vaccination lies in the ability to enhance both the humoral and cellular immune responses by adjuvants. Herein, self-assembled nanoparticles based on graphene oxide quantum dots with components of carnosine, resiquimod and Zn2+ ions, namely ZnGC-R, are designed as a new adjuvant for influenza vaccine. With its high capability for antigen-loading, ZnGC-R enhances antigen utilization, improves DC recruitment, and activates antigen-presenting cells. Single cell analysis of lymphocytes after intramuscular vaccination revealed that ZnGC-R generated multifaceted immune responses. ZnGC-R stimulated robust CD4+CCR7loPD-1hi Tfh and durable CD8+CD44hiCD62L- TEM immune responses, and simultaneously promoted the proliferation of CD26+ germinal center B cells. Besides, ZnGC-R elicited 2.53-fold higher hemagglutination-inhibiting antibody than commercial-licensed aluminum salt adjuvant. ZnGC-R based vaccine induced 342% stronger IgG antibody responses compared with vaccines with inactivated virus alone, leading to 100% in vivo protection efficacy against the H1N1 influenza virus challenge.

Synthesis of Imidazole-Based Deep Eutectic Solvents as Solid Lubricants: Lubricated State Transition.

The controllable character of the melting point of deep eutectic solvents (DESs) makes it easy to realize lubricated state transitions and produce excellent lubricating properties during friction. In this work, a series of novel imidazole-based DESs were synthesized to present a room-temperature solid state by shifting its eutectic point. Tribological test results show that the wear volume of these DESs decreases as the alkyl chains of the hydrogen bond donors increase. A proper deviation of the eutectic point in DESs produces stable lubricating properties. The present work provides a novel and simple method to prepare solid lubricants and enriches the use of DESs as lubricants. Simultaneously, the method expected to replace the use of conventional cutting fluids.

The functions and mechanisms of post-translational modification in protein regulators of RNA methylation: Current status and future perspectives.

RNA methylation, an epigenetic modification that does not alter gene sequence, may be important to diverse biological processes. Protein regulators of RNA methylation include "writers," "erasers," and "readers," which respectively deposit, remove, and recognize methylated RNA. RNA methylation, particularly N6-methyladenosine (m6A), 5-methylcytosine (m5C), N3-methylcytosine (m3C), N1-methyladenosine (m1A) and N7-methylguanosine (m7G), has been suggested as disease therapeutic targets. Despite advances in the structure and pharmacology of RNA methylation regulators that have improved drug discovery, regulating these proteins by various post-translational modifications (PTMs) has received little attention. PTM modifies protein structure and function, affecting all aspects of normal biology and pathogenesis, including immunology, cell differentiation, DNA damage repair, and tumors. It is becoming evident that RNA methylation regulators are also regulated by diverse PTMs. PTM of RNA methylation regulators induces their covalent linkage to new functional groups, hence modifying their activity and function. Mass spectrometry has identified many PTMs on protein regulators of RNA methylation. In this review, we describe the functions and PTM of protein regulators of RNA methylation and summarize the recent advances in the regulatory mode of human disease and its underlying mechanisms.

Protection of high-frequency low-intensity pulsed electric fields and brain-derived neurotrophic factor for SH-SY5Y cells against hydrogen peroxide-induced cell damage.

Neurodegenerative diseases (NDDs) pose a significant global health threat. In particular, Alzheimer disease, the most common type causing dementia, remains an incurable disease. Alzheimer disease is thought to be associated with an imbalance of reactive oxygen species (ROS) in neurons, and scientists considered ROS modulation as a promising strategy for novel remedies. In the study, human neural cell line SH-SY5Y was used in probing the effect of combining noninvasive high-frequency low-intensity pulsed electric field (H-LIPEF) and brain-derived neurotrophic factor (BDNF) in protection against hydrogen peroxide (H2O2)-induced neuron damage. Our result finds that the combination approach has intensified the neuroprotective effect significantly, perhaps due to H-LIPEF and BDNF synergistically increasing the expression level of the phosphorylated epidermal growth factor receptor (p-EGFR), which induces the survival-related mitogen-activated protein kinases (MAPK) proteins. The study confirmed the activation of extracellular signal-regulated kinase (ERK) and the downstream pro-survival and antioxidant proteins as the mechanism underlying neuron protection. These findings highlighted the potential of H-LIPEF combined with BDNF in the treatment of NDDs. Furthermore, BDNF-mimetic drugs combining with noninvasive H-LIPEF to patients is a promising approach worthy of further research. This points to strategies for selecting drugs to cooperate with electric fields in treating neurodegenerative disorders.

Superparamagnetic Composite Nanobeads Anchored with Molecular Glues for Ultrasensitive Label-free Proteomics.

Mass spectrometry has emerged as a mainstream technique for label-free proteomics. However, proteomic coverage for trace samples is constrained by adsorption loss during repeated elution at sample pretreatment. Here, we demonstrated superparamagnetic composite nanoparticles functionalized with molecular glues (MGs) to enrich proteins in trace human biofluid. We showed high protein binding (>95 %) and recovery (≈90 %) rates by anchor-nanoparticles. We further proposed a Streamlined Workflow based on Anchor-nanoparticles for Proteomics (SWAP) method that enabled unbiased protein capture, protein digestion and pure peptides elution in one single tube. We demonstrated SWAP to quantify over 2500 protein groups with 100 HEK 293T cells. We adopted SWAP to profile proteomics with trace aqueous humor samples from cataract (n=15) and wet age-related macular degeneration (n=8) patients, and quantified ≈1400 proteins from 5 µL aqueous humor. SWAP simplifies sample preparation steps, minimizes adsorption loss and improves protein coverage for label-free proteomics with previous trace samples.

Preparing and Wear-Resisting Property of Al2O3/Cu Composite Material Enhanced Using Novel In Situ Generated Al2O3 Nanoparticles.

Al2O3/Cu composite material (ACCM) are highly suitable for various advanced applications owing to its excellent properties. In the present work, a combination of the solution combustion synthesis and hydrogen reduction method was first employed to prepare Al2O3/Cu composite powder (ACCP), and subsequently ACCM was prepared by employing spark plasma sintering (SPS) technique. The effect of Al2O3 contents and SPS temperatures on the properties (relative density, hardness, friction coefficient, and electrical conductivity, et al.) of ACCM were investigated in detail. The results indicated that ACCM was very dense, and microstructure was consisted of fine Al2O3 particles evenly distributed in the Cu matrix. With the increase of SPS temperature, the relative density and hardness of ACCM had first increased and then decreased. At 775 °C, the relative density and hardness had attained the maximum values of 98.19% and 121.4 HV, respectively. With the increase of Al2O3 content, although the relative density of ACCM had gradually decreased, nevertheless, its friction coefficient had increased. Moreover, with the increase of Al2O3 contents, the hardness of ACCM first increased and then decreased, and reached the maximum value (121.4 HV) with 3 wt.% addition. On the contrary, the wear rate of ACCM had first decreased and then increased with the increase of Al2O3 contents, and attained the minimum (2.32 × 10-5 mm3/(N.m)) with 3 wt.% addition.

Thermal cycling-hyperthermia ameliorates Aß25-35-induced cognitive impairment in C57BL/6 mice.

Despite continuation of some controversies, Alzheimer's disease (AD), the most common cause of dementia nowadays, has been widely believed to derive mainly from excessive ß-amyloid (Aß) aggregation, that would increase reactive oxygen species (ROS) and induce neuroinflammation, leading to neuron loss and cognitive impairment. Existing drugs on Aß have been ineffective or offer only temporary relief at best, due to blood-brain barrier or severe side effects. The study employed thermal cycling-hyperthermia (TC-HT) to ease the Aß-induced cognitive impairments and compared its effect with continuous hyperthermia (HT) in vivo. It established an AD mice model via intracerebroventricular (i.c.v.) injection of Aß25-35, proving that TC-HT is much more effective in alleviating its performance decline in Y-maze and novel object recognition (NOR) tests, in comparison with HT. In addition, TC-HT also exhibits a better performance in decreasing the hippocampal Aß and ß-secretase (BACE1) expressions as well as the neuroinflammation markers-ionized calcium-binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) levels. Furthermore, the study finds that TC-HT can elevate more protein expressions of insulin degrading enzyme (IDE) and antioxidative enzyme superoxide dismutase 2 (SOD2) than HT. In sum, the study proves the potential of TC-HT in AD treatment, which can be put into application with the use of focused ultrasound (FUS).

Thickness measurement of cell walls of closed-cell foams in micro-CT images.

Characterising the microstructure of foams is an important task for improving foam manufacturing processes and building foam numerical models. This study proposed a method for measuring the thickness of individual cell walls of closed-cell foams in micro-CT images. It comprises a distance transform on CT images to obtain thickness information of cell walls, a watershed transform on the distance matrix to locate the midlines of cell walls, identifying the intersections of midlines of cell walls by examining how many regions each pixel on the midlines of cell walls connects with, disconnecting and numbering the midlines of cell walls, extracting the distance values of the pixels on the midlines (or midplanes) of cell walls, and calculating the thickness of individual cell walls by multiplying the extracted distance values by two. Using this method, the thickness of cell walls of a polymeric closed-cell foam was measured. It was found that cell wall thickness measured in 2D images shows larger average values (around 1.5 times) and dispersion compared to that measured in volumetric images.

Liquid biopsy on the horizon in immunotherapy of non-small cell lung cancer: current status, challenges, and perspectives.

Non-small cell lung cancer (NSCLC) is one of the most threatening malignancies to human health and life. In most cases, patients with NSCLC are already at an advanced stage when they are diagnosed. In recent years, lung cancer has made great progress in precision therapy, but the efficacy of immunotherapy is unstable, and its response rate varies from patient to patient. Several biomarkers have been proposed to predict the outcomes of immunotherapy, such as programmed cell death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB). Nevertheless, the detection assays are invasive and demanding on tumor tissue. To effectively predict the outcomes of immunotherapy, novel biomarkers are needed to improve the performance of conventional biomarkers. Liquid biopsy is to capture and detect circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and exosomes in body fluids, such as blood, saliva, urine, pleural fluid and cerebrospinal fluid as samples from patients, so as to make analysis and diagnosis of cancer and other diseases. The application of liquid biopsy provides a new possible solution, as it has several advantages such as non-invasive, real-time dynamic monitoring, and overcoming tumor heterogeneity. Liquid biopsy has shown predictive value in immunotherapy, significantly improving the precision treatment of lung cancer patients. Herein, we review the application of liquid biopsy in predicting the outcomes of immunotherapy in NSCLC patients, and discuss the challenges and future directions in this field.

Hepatitis B virus X protein induces p16 gene promoter methylation through upregulation of DNA methylation transferases DNMT1 and DNMT3A.

BACKGROUND: As a tumor suppressor, p16 can competitively block the cyclin D1-CDK4/6 complex to arrest the cell cycle in the G1 phase. Lack of p16 gene expression can lead to infinite cell proliferation and malignant transformation. OBJECTIVES: To determine whether the hepatitis B virus X protein (HBx) regulates the methylation and expression of the p16 gene. MATERIAL AND METHODS: We constructed a eukaryotic expression vector carrying the HBx gene and green fluorescent protein (GFP), and transfected it into HepG2 cells to build cell lines stably expressing GFP and GFP-HBx. The p16 protein level and p16 gene methylation were measured in these cell lines. We further detected the mRNA expression of DNA methyltransferases (DNMTs) 1, 3A and 3B. The DNMT1, DNMT3A and DNMT3B gene promoter sequences were inserted into a reporter vector (pGL3-Basic) to build recombinant vectors, which were then transiently transfected into different cell lines. After 48 h, the luciferase activity was measured. RESULTS: The level of p16 protein in GFP-HBx/HepG2 cells was significantly lower than in HepG2 and GFP/HepG2 cells. The CpG methylation was present in the p16 gene promoter region of GFP-HBx/HepG2 cells. The DNMT1 and DNMT3A mRNA levels in GFP-HBx/HepG2 cells were significantly elevated compared to that in the HepG2 cells (p = 0.0495). The luciferase activity in GFP-HBx/HepG2 cells transfected with the pGL3-DNMT1/3A pro plasmid was significantly higher than in HepG2 and GFP/HepG2 cells (both p < 0.05). CONCLUSIONS: The HBx can induce p16 gene promoter methylation and inhibit the expression of p16 in HepG2 cells. This occurs due to HBx activation of DNMT1 and DNMT3A promoters and the induction of p16 promoter methylation, which downregulates the expression of p16 protein.

Neutrophil side fluorescence: a new indicator for predicting the severity of patients with bronchiectasis.

BACKGROUND: Neutrophilic inflammation in the airway is a hallmark of bronchiectasis. Neutrophil extracellular traps (NETs) have been reported to play an important role in the occurrence and development of bronchiectasis. Neutrophil side fluorescence is one of the characteristics of neutrophils that can reflect the activation of neutrophils and the formation of NETs. OBJECTIVE: To explore the relationship between the values of neutrophil side fluorescence (NEUT-SFL) in the peripheral blood of bronchiectasis patients, and the severity of the disease. METHODS: 82 patients with bronchiectasis from the Department of Respiratory and Critical Medicine, at the Third Affiliated Hospital of Southern Medical University and were scored with Bronchiectasis Severity Index (BSI) (2019-2021). The clinical data such as the value of NEUT-SFL, neutrophil count, C-reactive protein, and procalcitonin levels were collected and retrospectively analyzed. NEUT-SFL values neutrophil count from 28 healthy subjects were also used to ascertain cut-off values. RESULTS: Based on the BSI scores, patients were divided into three categories as mild (32%), moderate (29%), and severe (39%). Our results showed that the values of NEUT-SFL were higher in bronchiectasis patients compared to healthy controls. The levels of NEUT-SFL positively correlated with the high BSI scores in patients (P = 0.037, r = 0.23) and negatively correlated with the lung function in these patients (r = - 0.35, P = 0.001). The area under the ROC curve was 0.813, the best cut-off was 42.145, indicating that NEUT-SFL values > 42.145 can potentially predict the severity of bronchiectasis. CONCLUSIONS: The values of NEUT-SFL in the peripheral blood can be used for predicting the severity of bronchiectasis.

Chloride intercellular channel 3 suppression-mediated macrophage polarization: a potential indicator of poor prognosis of hepatitis B virus-related acute-on-chronic liver failure.

Patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) are characterized by immune paralysis and susceptibility to infections. Macrophages are important mediators of immune responses can be subclassified into two main phenotypes: classically activated and alternatively activated. However, few studies have investigated changes to macrophage polarization in HBV-related liver diseases. Therefore, we investigated the functional status of monocyte-derived macrophages (MDMs) from patients with mild chronic hepatitis B (n = 226), HBV-related compensated cirrhosis (n = 36), HBV-related decompensated cirrhosis (n = 40), HBV-ACLF (n = 62) and healthy controls (n = 10), as well as Kupffer cells (KCs) from patients with HBV-ACLF (n = 3). We found that during the progression of HBV-related liver diseases, the percentage of CD163+ CD206+ macrophages increased, while the percentage of CD80+ human leukocyte antigen-DR+ macrophages decreased significantly. MDMs and KCs mainly exhibited high CD163+ CD206+ expression in patients with HBV-ACLF, which predicted poor clinical outcome and higher liver transplantation rate. Transcriptome sequencing analysis revealed that chloride intracellular channel-3 (CLIC3) was reduced in patients with HBV-ACLF, indicating a poor prognosis. To further study the effect of CLIC3 on macrophage polarization, human monocytic THP-1 cell-derived macrophages were used. We found that classical and alternative macrophage activation occurred through nuclear factor kappa B (NF-κB) and phosphoinositide 3-kinase/protein kinase B pathways, respectively. CLIC3 suppression inhibited NF-κB activation and promoted the alternative activation. In conclusion, macrophage polarization gradually changed from classically activated to alternatively activated as HBV-related liver diseases progressed. Both CLIC3 suppression and increased alternatively activated macrophage percentage were potential indicators of the poor prognosis of patients with HBV-ACLF.

Thermoelectric properties of Zn- and Ce-alloyed In2O3and the effect of SiO2nanoparticle additives.

Thermoelectric materials are considered promising candidates for thermal energy conversion. This study presents the fabrication of Zn- and Ce-alloyed In2O3with a porous structure. The electrical conductivity was improved by the alloying effect and an ultra-low thermal conductivity was observed owing to the porous structure, which concomitantly provide a distinct enhancement ofZT. However, SiO2nanoparticle additives react with the matrix to form a third-phase impurity, which weakens the electrical conductivity and increases the thermal conductivity. A thermoelectric module was constructed for the purpose of thermal heat energy conversion. Our experimental results proved that both an enhancement in electrical conductivity and a suppression in thermal conductivity could be achieved through nano-engineering. This approach presents a feasible route to synthesize porous thermoelectric oxides, and provides insight into the effect of additives; moreover, this approach is a cost-effective method for the fabrication of thermoelectric oxides without traditional hot-pressing and spark-plasma-sintering processes.

Identification of Candidate Genes Associated With Hypoxia Tolerance in Trachinotus blochii Using Bulked Segregant Analysis and RNA-Seq.

Golden Pompano (Trachinotus blochii) has rapidly developed into the one of the main valuable fish species in Chinese marine aquaculture. Due to its rapid growth, active metabolism, and high oxygen consumption, hypoxia will increase its mortality and cause serious economic losses. We constructed two experimental groups of fish with different degrees of tolerance to hypoxia, used BSR-Seq analysis based on genome and genetic linkage groups to locate SNPs and genes that were related to the differences in hypoxia tolerance. The results showed that hypoxia tolerance SNPs of golden pompano may be jointly determined by multiple linkage groups, especially linkage groups 18 and 22. There were 768 and 348 candidate genes located in the candidate regions of the brain and liver, respectively. These genes were mainly involved in anaerobic energy metabolism, stress response, immune response, waste discharge, and cell death. The prostaglandin-endoperoxide synthase 2 (PTGS2) on LG8, which is involved in the metabolism of arachidonic acid, has a G/A nonsynonymous mutation at position 20641628, and the encoded amino acid was changed from hydrophobic aspartic acid to asparaginate. The specific pathway of the RIG-I-like receptor signaling pathway in the liver may mediate the metabolic system and the immune system, linking glucose metabolism with immune regulation. The death of the hypoxia-intolerant group may be due to the accumulation of lactic acid caused by the activation of anaerobic glycolysis during the early stage of hypoxia stress, and the activation of type I interferon was inhibited, which resulted in decreased immunity. Among the genes involved in the RIG-I-like receptor signaling pathway, the CYLD Lysine 63 Deubiquitinase (CYLD) located on LG16 had a G/T nonsynonymous mutation at position 13629651, and the encoded amino acid was changed from alanine acid to valine. The interferon induced with helicase C domain 1 (Ifih1) located on LG18 has a G/C nonsynonymous mutation at position 16153700, and the encoded hydrophilic glycine was changed to hydrophobic alanine. Our findings suggest these SNPs may assist in the molecular breeding of hypoxia-tolerant golden pompano, and speculate that the balance of glucose and lipid metabolism plays a key role in Trachinotus blochii under acute hypoxia.

The 96-week clinical outcomes after cessation of nucleos(t)ide analog treatment in chronic hepatitis B patients.

BACKGROUND: Chronic hepatitis B (CHB) patients have a high virological relapse rate after cessation of nucleos(t)ide analog (NA) treatment, but the clinical outcome remains unclear. This study aimed to investigate the 96-week clinical outcomes and the risk factors for relapse in CHB after cessation of NAs. METHODS: This study was a prospective trial; 74 eligible patients were enrolled. The patients underwent NA cessation and follow-up according to the 2012 Asian Pacific Association for the Study of the Liver Guideline. Symptoms, biochemical (aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, urea nitrogen, creatinine), virological data (hepatitis B surface antigen [HBsAg], hepatitis B e antigen [HBeAg], hepatitis B e antibody [HBeAb], hepatitis B virus [HBV] DNA levels), and color Doppler ultrasound examination results were recorded and analysed. RESULTS: After NA cessation, 19 cases were HBsAg-negative without relapse during the 96-week follow-up. Of the 55 cases of HBsAg-positive after cessation, four types of clinical outcomes were observed. Twelve patients had no relapse during the 96-week follow-up (type A, 21.8%), 7 patients underwent virological relapses but spontaneously had a non-virological relapse (type B, 12.7%), 10 patients maintained virological relapse (type C, 18.2%), and 26 patients turned to clinical relapse, received NA retreatment, and achieved ALT normalization and negative conversion of HBV DNA within 12 months (type D, 47.3%). The 2-year overall cumulative rates of virological and clinical relapses were 58.1% and 24.3%, respectively. Independent factors associated with virological relapse were duration of negative HBV DNA, EOT (end of treatment) HBsAg, and original status of HBeAg. The EOT HBsAg was also an independent factor for clinical relapse. CONCLUSIONS: There are four types of clinical outcomes in patients with CHB after cessation of NA treatment. Further research is needed to explore the mechanism of different clinical outcomes. The EOT HBsAg level is an independent factor associated with both virological and clinical relapse.

Real-time interactive artificial intelligence of things-based prediction for adverse outcomes in adult patients with pneumonia in the emergency department.

BACKGROUND: Artificial intelligence of things (AIoT) may be a solution for predicting adverse outcomes in emergency department (ED) patients with pneumonia; however, this issue remains unclear. Therefore, we conducted this study to clarify it. METHODS: We identified 52,626 adult ED patients with pneumonia from three hospitals between 2010 and 2019 for this study. Thirty-three feature variables from electronic medical records were used to construct an artificial intelligence (AI) model to predict sepsis or septic shock, respiratory failure, and mortality. After comparisons of the predictive accuracies among logistic regression, random forest, support-vector machine (SVM), light gradient boosting machine (LightGBM), multilayer perceptron (MLP), and eXtreme Gradient Boosting (XGBoost), we selected the best one to build the model. We further combined the AI model with the Internet of things as AIoT, added an interactive mode, and implemented it in the hospital information system to assist clinicians with decision making in real time. We also compared the AIoT-based model with the confusion-urea-respiratory rate-blood pressure-65 (CURB-65) and pneumonia severity index (PSI) for predicting mortality. RESULTS: The best AI algorithms were random forest for sepsis or septic shock (area under the curve [AUC] = 0.781), LightGBM for respiratory failure (AUC = 0.847), and mortality (AUC = 0.835). The AIoT-based model represented better performance than CURB-65 and PSI indicators for predicting mortality (0.835 vs. 0.681 and 0.835 vs. 0.728). CONCLUSIONS: A real-time interactive AIoT-based model might be a better tool for predicting adverse outcomes in ED patients with pneumonia. Further validation in other populations is warranted.