Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders: progress of experimental models based on disease pathogenesis.

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction. To date, no effective treatment exists as the exact causative mechanism remains unknown. Therefore, experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets. Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4, which is highly expressed on the membrane of astrocyte endfeet, most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes. These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders, such as aquaporin-4 loss, astrocytopathy, granulocyte and macrophage infiltration, complement activation, demyelination, and neuronal loss; however, they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders. In this review, we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro, ex vivo, and in vivo for neuromyelitis optica spectrum disorders, suggest potential pathogenic mechanisms for further investigation, and provide guidance on experimental model choices. In addition, this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders, offering further therapeutic targets and a theoretical basis for clinical trials.

The 14-3-3 protein nt GF14e interacts with CIPK2 and increases low potassium stress in tobacco.

Potassium (K+) plays a role in enzyme activation, membrane transport, and osmotic regulation processes. An increase in potassium content can significantly improve the elasticity and combustibility of tobacco and reduce the content of harmful substances. Here, we report that the expression analysis of Nt GF14e, a 14-3-3 gene, increased markedly after low-potassium treatment (LK). Then, chlorophyll content, POD activity and potassium content, were significantly increased in overexpression of Nt GF14e transgenic tobacco lines compared with those in the wild type plants. The net K+ efflux rates were severely lower in the transgenic plants than in the wild type under LK stress. Furthermore, transcriptome analysis identified 5708 upregulated genes and 2787 downregulated genes between Nt GF14e overexpressing transgenic tobacco plants. The expression levels of some potassium-related genes were increased, such as CBL-interacting protein kinase 2 (CIPK2), Nt CIPK23, Nt CIPK25, H+-ATPase isoform 2 a (AHA2a), Nt AHA4a, Stelar K+ outward rectifier 1(SKOR1), and high affinity K+ transporter 5 (HAK5). The result of yeast two-hybrid and luciferase complementation imaging experiments suggested Nt GF14e could interact with CIPK2. Overall, these findings indicate that NtGF14e plays a vital roles in improving tobacco LK tolerance and enhancing potassium nutrition signaling pathways in tobacco plants.

A bimetallic sulfide FeCoS4@rGO hybrid as a high-performance anode for potassium-ion batteries.

We synthesized a low metal-to-sulfur atomic ratio (0.5) FeCoS4, exhibiting high reversible specific capacity. Reduced graphene oxide was covered on the surface to improve the cycling stability and rate performance further. Density functional theory calculations show that composite materials can effectively increase the adsorption energy and enhance the diffusion kinetics.

Transcriptomic analysis reveals the crosstalk between type 2 diabetes and chronic pancreatitis.

Background and Aims: Mounting evidence highlights a strong association between chronic pancreatitis (CP) and type 2 diabetes (T2D), although the exact mechanism of interaction remains unclear. This study aimed to investigate the crosstalk genes and pathogenesis between CP and T2D. Methods: Transcriptomic gene expression profiles of CP and T2D were extracted from Gene Expression Omnibus, respectively, and the common differentially expressed genes (DEGs) were subsequently identified. Further analysis, such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction, transcription factors (TFs), microRNA (miRNAs), and candidate chemicals identification, was performed to explore the possible common signatures between the two diseases. Results: In total, we acquired 281 common DEGs by interacting CP and T2D datasets, and identified 10 hub genes using CytoHubba. GO and KEGG analyses revealed that endoplasmic reticulum stress and mitochondrial dysfunction were closely related to these common DEGs. Among the shared genes, EEF2, DLD, RAB5A, and SLC30A9 showed promising diagnostic value for both diseases based on receiver operating characteristic curve and precision-recall curves. Additionally, we identified 16 key TFs and 16 miRNAs that were strongly correlated with the hub genes, which may serve as new molecular targets for CP and T2D. Finally, candidate chemicals that might become potential drugs for treating CP and T2D were screened out. Conclusion: This study provides evidence that there are shared genes and pathological signatures between CP and T2D. The genes EEF2, DLD, RAB5A, and SLC30A9 have been identified as having the highest diagnostic efficiency and could be served as biomarkers for these diseases, providing new insights into precise diagnosis and treatment for CP and T2D.

An Amino Acids and Dipeptide Injection Inhibits the TNF-α/HMGB1 Inflammatory Signaling Pathway to Reduce Pyroptosis and M1 Microglial Polarization in POCD Mice: the Gut to the Brain.

Peripheral surgery-induced neural inflammation is a key pathogenic mechanism of postoperative cognitive dysfunction (POCD). However, the mechanism underlying neuroinflammation and associated neural injury remains elusive. Surgery itself can lead to gut damage, and the occurrence of POCD is accompanied by high levels of TNF-α in the serum and blood‒brain barrier (BBB) damage. Reductions in stress, inflammation and protein loss have been emphasized as strategies for enhanced recovery after surgery (ERAS). We designed an amino acids and dipeptide (AAD) formula for injection that could provide intestinal protection during surgery. Through the intraoperative infusion of AAD based on the ERAS concept, we aimed to explore the effect of AAD injection on POCD and its underlying mechanism from the gut to the brain. Here, we observed that AAD injection ameliorated neural injury in POCD, in addition to restoring the function of the intestinal barrier and BBB. We also found that TNF-α levels decreased in the ileum, blood and hippocampus. Intestinal barrier protectors and TNF-α inhibitors also alleviated neural damage. AAD injection treatment decreased HMGB1 production, pyroptosis, and M1 microglial polarization and increased M2 polarization. In vitro, AAD injection protected the impaired gut barrier and decreased TNF-α production, alleviating damage to the BBB by stimulating cytokine transport in the body. HMGB1 and Caspase-1 inhibitors decreased pyroptosis and M1 microglial polarization and increased M2 polarization to protect TNF-α-stimulated microglia in vitro. Collectively, these findings suggest that the gut barrier-TNF-α-BBB-HMGB1-Caspase-1 inflammasome-pyroptosis-M1 microglia pathway is a novel mechanism of POCD related to the gut-brain axis and that intraoperative AAD infusion is a potential treatment for POCD.

Population exposure to emerging perfluoroalkyl acids (PFAAs) via drinking water resources: Application of multivariate statistics and risk assessment models.

This study assessed the occurrence, origins, and potential risks of emerging perfluoroalkyl acids (PFAAs) for the first time in drinking water resources of Khyber Pakhtunkhwa, Pakistan. In total, 13 perfluoroalkyl carboxylic acids (PFCAs) with carbon (C) chains C4-C18 and 4 perfluoroalkyl sulfonates (PFSAs) with C chains C4-C10 were tested in both surface and ground drinking water samples using a high-performance liquid chromatography system (HPLC) equipped with an Agilent 6460 Triple Quadrupole liquid chromatography-mass spectrometry (LC-MS) system. The concentrations of ∑PFCAs, ∑PFSAs, and ∑PFAAs in drinking water ranged from 1.46 to 72.85, 0.30-8.03, and 1.76-80.88 ng/L, respectively. Perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), and perfluoropentanoic acid (PFPeA) were the dominant analytes in surface water followed by ground water, while the concentration of perfluorobutane sulfonate (PFBS), perfluorooctanoic acid (PFOA), perfluoroheptanoic acid (PFHpA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) were greater than long-chain PFOA and PFOS. The correlation statistics, which showed a strong correlation (p < 0.05) between the PFAA analytes, potentially indicated the fate of PFAAs in the area's drinking water sources, whereas the hierarchical cluster analysis (HCA) and principal component analysis (PCA) statistics identified industrial, domestic, agricultural, and commercial applications as potential point and non-point sources of PFAA contamination in the area. From risk perspectives, the overall PFAA toxicity in water resources was within the ecological health risk thresholds, where for the human population the hazard quotient (HQ) values of individual PFAAs were < 1, indicating no risk from the drinking water sources; however, the hazard index (HI) from the ∑PFAAs should not be underestimated, as it may significantly result in potential chronic toxicity to exposed adults, followed by children.

SlCarE054 in Spodoptera litura (Lepidoptera: Noctuidae) showed direct metabolic activity to ß-cypermethrin with stereoselectivity.

Carboxylesterases (CarEs) is an important detoxification enzyme system in phase Ⅰ participating in insecticides resistance. In our previous study, SlCarE054, a CarEs gene from lepidoptera class, was screened out to be upregulated in a pyrethroids and organophosphates resistant population. Its overexpression was verified in two field-collected populations of Spodoptera litura (Lepidoptera: Noctuidae) resistant to pyrethroids and organophosphates by qRT-PCR. Spatiotemporal expression results showed that SlCarE054 was highly expressed in the pupae stage and the digestive tissue midgut. To further explore its role in pyrethroids and organophosphates resistance, its metabolism activity to insecticides was determined by UPLC. Its recombinant protein showed significant metabolism activity to cyhalothrin and fenvalerate, but not to phoxim or chlorpyrifos. The metabolic activity of SlCarE054 to ß-cypermethrin showed stereoselectivity, with higher metabolic activity to θ-cypermethrin than the enantiomer α-cypermethrin. The metabolite of ß-cypermethrin was identified as 3-phenoxybenzaldehyde. Further modelling and docking analysis indicated that ß-cypermethrin, cyhalothrin and fenvalerate could bind with the catalytic triad of the 3D structure of SlCarE054. The interaction of ß-cypermethrin with SlCarE054 also showed the lowest binding energy. Our work provides evidence that SlCarE054 play roles in ß-cypermethrin resistance in S. litura.

A multi-channel electrochemical biosensor based on polyadenine tetrahedra for the detection of multiple drug resistance genes.

Antimicrobial resistance poses a serious threat to human health due to the high morbidity and mortality caused by drug-resistant microbial infections. Therefore, the development of rapid, sensitive and selective identification methods is key to improving the survival rate of patients. In this paper, a sandwich-type electrochemical DNA biosensor based on a polyadenine-DNA tetrahedron probe was constructed. The key experimental conditions were optimized, including the length of polyadenine, the concentration of the polyadenine DNA tetrahedron, the concentration of the signal probe and the hybridization time. At the same time, poly-avidin-HRP80 was used to enhance the electrochemical detection signal. Finally, excellent biosensor performance was achieved, and the detection limit for the synthetic DNA target was as low as 1 fM. In addition, we verified the practicability of the system by analyzing E. coli with the MCR-1 plasmid and realized multi-channel detection of the drug resistance genes MCR-1, blaNDM, blaKPC and blaOXA. With the ideal electrochemical interface, the polyA-based biosensor exhibits excellent stability, which provides powerful technical support for the rapid detection of antibiotic-resistant strains in the field.

Effect of Raltitrexed on ECA109 Cellular Radiosensitivity and Its Mechanism in Esophageal Cancer.

BACKGROUND: To investigate the effect of raltitrexed + X-ray irradiation on esophageal cancer ECA109 cells and analyze the potential action mechanism. METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to analyze the inhibitory effect of raltitrexed on cell proliferation. The effect of raltitrexed on radiosensitivity was studied through a clone-forming experiment. The scratch assay and invasion test were performed to understand the cell migration and invasion abilities. The apoptosis rate change was measured using a flow cytometer, and Western Blotting was used to determine the expression of B cell lymphoma-2 (Bcl-2) and Bcl2-associated X protein (Bax) in each group. RESULTS: Raltitrexed significantly inhibited ECA109 proliferation in a time-dose-dependent manner; there were significant differences among different concentrations and times of action. The results of the clone-forming experiment showed a sensitization enhancement ratio of 1.65, and this demonstrated a radiosensitization effect. After the combination of raltitrexed with X-ray, the cell migration distance was shortened, and the number of cells penetrating the membrane was reduced. CONCLUSION: Raltitrexed can inhibit the growth of esophageal cancer ECA109 cells and has a radiosensitization effect.

Clinical and Molecular Characteristics of Patients with Bloodstream Infections Caused by KPC and NDM Co-Producing Carbapenem-Resistant Klebsiella pneumoniae.

Purpose: Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-ß-lactamase (NDM) co-producing carbapenem-resistant Klebsiella pneumoniae (KPC-NDM-CRKP) isolates have been increasingly reported worldwide but have not yet been systematically studied. Thus, we have conducted a study to compare the risk factors, molecular characteristics, and mortality involved in clinical bloodstream infections (BSIs) caused by KPC-NDM-CRKP and KPC-CRKP strains. Methods: A retrospective study was conducted on 231 patients with BSIs caused by CRKP at Jinling Hospital in China from January 2020 to December 2022. Antimicrobial susceptibility testing, carbapenemase genes detection and whole-genome sequencing were performed subsequently. Results: Overall, 231 patients were included in this study: 25 patients with KPC-NDM-CRKP BSIs and 206 patients with KPC-CRKP BSIs. Multivariate analysis implicated ICU-acquired BSI, surgery within 30 days, and longer stay of hospitalization prior to CRKP isolation as independent risk factors for KPC-NDM-CRKP BSIs. The 30-day mortality rate of the KPC-NDM-CRKP BSIs group was 56% (14/25) compared with 32.5% (67/206) in the KPC-CRKP BSIs control group (P = 0.02). The ICU-acquired BSIs, APACHE II score at BSI onset, and BSIs caused by KPC-NDM-CRKP were independent predictors for 30-day mortality in patients with CRKP bacteremia. The most prevalent ST in KPC-NDM-CRKP isolates was ST11 (23/25, 92%), followed by ST15 (2/25, 8%). Conclusion: In patients with CRKP BSIs, KPC-NDM-CRKP was associated with an excess of mortality. The likelihood that KPC-NDM-CRKP will become the next "superbug" highlights the significance of epidemiologic surveillance and clinical awareness of this pathogen.

The pattern of tumor progression on first-line immune checkpoint inhibitor-based systemic therapy for Chinese advanced hepatocellular carcinoma -CLEAP 004 study.

Background: For decades, stratification criteria for first-line clinical studies have been highly uniform. However, there is no principle or consensus for restratification after systemic treatment progression based on immune checkpoint inhibitors (ICIs). The aim of this study was to assess the patterns of disease progression in patients with advanced hepatocellular carcinoma (HCC) who are not eligible for surgical intervention, following the use of immune checkpoint inhibitors. Methods: This is a retrospective study that involved patients with inoperable China liver stage (CNLC) IIIa and/or IIIb. The patients were treated at eight centers across China between January 2017 and October 2022. All patients received at least two cycles of first-line treatment containing immune checkpoint inhibitors. The patterns of disease progression were assessed using RECIST criteria 1.1. Different progression modes have been identified based on the characteristics of imaging progress. The study's main outcome measures were post-progression survival (PPS) and overall survival (OS). Survival curves were plotted using the Kaplan-Meier method to compare the difference among the four groups. Subgroup analysis was conducted to compare the efficacy of different immunotherapy combinations. Variations in the efficacy of immunotherapy have also been noted across patient groups exhibiting alpha-fetoprotein (AFP) levels equal to or exceeding 400ng/mL, in contrast to those with AFP levels below 400ng/mL. Results: The study has identified four distinct patterns of progress, namely p-IIb, p-IIIa, p-IIIb, and p-IIIc. Diverse patterns of progress demonstrate notable variations in both PPS and OS. The group p-IIb had the longest PPS of 12.7m (95% 9.3-16.1) and OS 19.6m (95% 15.6-23.5), the remaining groups exhibited p-IIIb at PPS 10.5 months (95%CI: 7.9-13.1) and OS 19.2 months (95%CI 15.1-23.3). Similarly, p-IIIc at PPS 5.7 months (95%CI: 4.2-7.2) and OS 11.0 months (95%CI 9.0-12.9), while p-IIIa at PPS 3.4 months (95%CI: 2.7-4.1) and OS 8.2 months (95%CI 6.8-9.5) were also seen. Additional stratified analysis was conducted and showed there were no differences of immunotherapy alone or in combination in OS (HR= 0.92, 95%CI: 0.59-1.43, P=0.68) and PPS (HR= 0.88, 95%CI: 0.57-1.36, P=0.54); there was no significant difference in PPS (HR=0.79, 95% CI: 0.55-1.12, P=0.15) and OS (HR=0.86, 95% CI: 0.61-1.24, P=0.39) for patients with AFP levels at or over 400ng/mL. However, it was observed that patients with AFP levels above 400ng/mL experienced a shorter median progression of PPS (8.0 months vs. 5.0 months) after undergoing immunotherapy. Conclusion: In this investigation of advanced hepatocellular carcinoma among Chinese patients treated with immune checkpoint inhibitors, we identified four distinct progression patterns (p-IIb, p-IIIa, p-IIIb and p-IIIc) that showed significant differences in PPS and OS. These findings demonstrate the heterogeneity of disease progression and prognosis after immunotherapy failure. Further validation in large cohorts is necessary to develop prognostic models that integrate distinct progression patterns to guide subsequent treatment decisions. Additionally, post-immunotherapy progression in patients with AFP levels ≥400ng/mL indicates a shortened median PPS. These findings provide valuable insights for future personalized treatment decisions.

Liposomes in the cosmetics: present and outlook.

Liposomes are small spherical vesicles composed of phospholipid bilayers capable of encapsulating a variety of ingredients, including water- and oil-soluble compound, which are one of the most commonly used piggybacking and delivery techniques for many active ingredients and different compounds in biology, medicine and cosmetics. With the increasing number of active cosmetic ingredients, the concomitant challenge is to effectively protect, transport, and utilize these substances in a judicious manner. Many cosmetic ingredients are ineffective both topically and systemically when applied to the skin, thus changing the method of delivery and interaction with the skin of the active ingredients is a crucial step toward improving their effectiveness. Liposomes can improve the delivery of active ingredients to the skin, enhance their stability, and ultimately, improve the efficacy of cosmetics and and pharmaceuticals. In this review, we summarized the basic properties of liposomes and their recent advances of functionalities in cosmetics and and pharmaceuticals. Also, the current state of the art in the field is discussed and the prospects for future research areas are highlighted. We hope that this review will provide ideas and inspiration on the application and development of cosmetics and pharmaceuticals.

Effect of polyethoxylated flavonoids (PMFs)-loaded citral and chitosan composite coatings on citrus preservation: From the perspective of fruit resistance.

Previous studies have shown that polymethoxylated flavonoids-loaded citral emulsion (PCT) can inhibit the growth and reproduction of Penicillium in citrus; however, PCT is difficult to apply to fruit preservation due to its high fluidity and volatility. Therefore, in this study, we combined PCT with chitosan (CS) to investigate the effect of a composite coating on citrus preservation. The results showed that compared to the control group, the CS-PCT group could effectively reduce the decay rate and maintain moisture availability, color difference, and hardness. Moreover, the contents of nonenzymatic antioxidants and volatile substances with antimicrobial activity were better preserved. In addition, the activities of related antioxidant enzymes were greater in the treatment group, and the expression of the corresponding enzyme-encoding genes was upregulated. Consequently, CS-PCT treatment could effectively maintain fruit quality and improve the resistance of citrus fruits during storage; moreover, it can be considered a nontoxic and efficient citrus preservative.

Optical enhancement mode 2 improves the detection rate of gastric neoplastic lesion in high-risk populations: A multicenter randomized controlled clinical study.

OBJECTIVES: Detection of early neoplastic lesions is crucial for improving the survival rates of patients with gastric cancer. Optical enhancement mode 2 is a new image-enhanced endoscopic technique that offers bright images and can improve the visibility of neoplastic lesions. This study aimed to compare the detection of neoplastic lesions with optical enhancement mode 2 and white-light imaging (WLI) in a high-risk population. METHODS: In this prospective multicenter randomized controlled trial, patients were randomly assigned to optical enhancement mode 2 or WLI groups. Detection of suspicious neoplastic lesions during the examinations was recorded, and pathological diagnoses served as the gold standard. RESULTS: A total of 1211 and 1219 individuals were included in the optical enhancement mode 2 and WLI groups, respectively. The detection rate of neoplastic lesions was significantly higher in the optical enhancement mode 2 group (5.1% vs. 1.9%; risk ratio, 2.656 [95% confidence interval, 1.630-4.330]; p < 0.001). The detection rate of neoplastic lesions with an atrophic gastritis background was significantly higher in the optical enhancement mode 2 group (8.6% vs. 2.6%, p < 0.001). The optical enhancement mode 2 group also had a higher detection rate among endoscopists with different experiences. CONCLUSIONS: Optical enhancement mode 2 was more effective than WLI for detecting neoplastic lesions in the stomach, and can serve as a new method for screening early gastric cancer in clinical practice. CLINICAL REGISTRY: United States National Library of Medicine (https://www. CLINICALTRIALS: gov), ID: NCT040720521.

PHLDA1 contributes to hypoxic ischemic brain injury in neonatal rats via inhibiting FUNDC1-mediated mitophagy.

Hypoxia-ischemia (HI) is one of the main causes of neonatal brain injury. Mitophagy has been implicated in the degradation of damaged mitochondria and cell survival following neonatal brain HI injury. Pleckstrin homology-like domain family A member 1 (PHLDA1) plays vital roles in the progression of various disorders including the regulation of oxidative stress, the immune responses and apoptosis. In the present study we investigated the role of PHLDA1 in HI-induced neuronal injury and further explored the mechanisms underlying PHLDA1-regulated mitophagy in vivo and in vitro. HI model was established in newborn rats by ligation of the left common carotid artery plus exposure to an oxygen-deficient chamber with 8% O2 and 92% N2. In vitro studies were conducted in primary hippocampal neurons subjected to oxygen and glucose deprivation/-reoxygenation (OGD/R). We showed that the expression of PHLDA1 was significantly upregulated in the hippocampus of HI newborn rats and in OGD/R-treated primary neurons. Knockdown of PHLDA1 in neonatal rats via lentiviral vector not only significantly ameliorated HI-induced hippocampal neuronal injury but also markedly improved long-term cognitive function outcomes, whereas overexpression of PHLDA1 in neonatal rats via lentiviral vector aggravated these outcomes. PHLDA1 knockdown in primary neurons significantly reversed the reduction of cell viability and increase in intracellular reactive oxygen species (ROS) levels, and attenuated OGD-induced mitochondrial dysfunction, whereas overexpression of PHLDA1 decreased these parameters. In OGD/R-treated primary hippocampal neurons, we revealed that PHLDA1 knockdown enhanced mitophagy by activating FUNDC1, which was abolished by FUNDC1 knockdown or pretreatment with mitophagy inhibitor Mdivi-1 (25 µM). Notably, pretreatment with Mdivi-1 or the knockdown of FUNDC1 not only increased brain infarct volume, but also abolished the neuroprotective effect of PHLDA1 knockdown in HI newborn rats. Together, these results demonstrate that PHLDA1 contributes to neonatal HI-induced brain injury via inhibition of FUNDC1-mediated neuronal mitophagy.

Contributing Factors Affecting the Length of Hospital Stay among Febrile Patients with Omicron Reported in Suzhou.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has had global attention with regard to the urgent challenging threat to global public health. Currently, the novel Omicron variant is showing rapid transmission across the world, which appears to be more contagious than the previous variants of COVID-19. Early recognition of disease is critical for patients' prognosis. Fever is the most common symptom. We evaluated the clinical characteristics of febrile patients with COVID-19 reported in Suzhou and explored the predictors for a longer duration of hospitalization in febrile patients. METHODS: This retrospective study was carried out in 146 Omicron variant infected patients confirmed by nucleic acid tests in the Affiliated Infectious Hospital of Soochow University between February 13, 2022 and March 2, 2022. Data of febrile and afebrile laboratory-confirmed patients on hospital admission in Suzhou were collected and compared. According to the median length of stay (LOS), febrile cases were divided into short and long LOS groups. Then the predictive factors for a prolonged duration of hospitalization were analyzed using logistic regression methods. Receiver Operating Characteristic (ROC) Curve analysis was used to analyze the effectiveness of the risk factors for prolonged duration of hospitalization in febrile COVID-19 patients. RESULTS: Of the 146 discharged patients in our study, 112 patients (76.7%) caught a fever. Compared to afebrile Omicron patients, febrile patients showed a significantly longer duration of hospitalization (15.00 (5.80) vs. 13.00 (6.00), p = 0.002). Taking the median LOS (15 days) as the dividing point, 64 febrile cases were assigned to the short LOS group and the rest to the long LOS group. The long LOS group had a longer virus shedding duration than the short LOS group (18.42 ± 2.86 vs. 11.94 ± 2.50 days, p < 0.001). Compared to short LOS febrile patients, long LOS patients were older (44.88 ± 21.36 vs. 30.89 ± 17.95 years, p < 0.001) and showed a higher proportion of greater than 60 years old (33.3% vs. 9.4%, p = 0.002; Supplemental Table S2). Febrile patients with long LOS also showed a higher proportion of hypertension (25% vs. 6.3%, p = 0.005) and higher levels of cTnI (5.00 (3.00) vs. 4.00 (2.00) µg/L, p = 0.025). The multivariate analysis indicated that virus shedding duration (OR 2.369, 95% CI 1.684 - 3.333, p < 0.001) was the independent risk factor associated with long-term hospital stay in febrile patients with Omicron. Furthermore, ROC Curve analysis revealed that the area under the curve (AUC) for virus shedding duration to diagnose prolonged duration of hospitalization in febrile COVID-19 patients was 0.951 (95% CI 0.913 - 0.989). The cutoff point was set at 14.5 days. CONCLUSIONS: More than half of the non-severe patients exposed to the new Omicron variant had symptoms of fever. In total, 42.86% of the febrile patients were discharged within 15 days since hospital admission. Febrile Omicron cases took a longer duration of hospitalization compared to afebrile patients, and virus shedding duration (OR 2.369, 95% CI 1.684 - 3.333, p < 0.001) was probably a predictive factor for long-term hospital stays.

Propelling gold nanozymes: catalytic activity and biosensing applications.

Recently, gold nanomaterials have been rapidly developed owing to their high stability, good biocompatibility, and multifunctionality. The unique catalytic activity of gold nanomaterials has driven the emergence of the concept for a "gold nanozyme." Understanding the characteristics of gold nanozymes is crucial for improving their catalytic performance as well as expanding their applications. In this review, we provide an overview of the intrinsic enzyme-like activities of gold nanozymes, including peroxidase-, catalase-, superoxide dismutase-, and glucose oxidase-like activities, and the catalytic mechanisms involved. In addition, strategies for modulating the catalytic activity of gold nanozymes and their applications in biosensing were discussed in detail. Moreover, we highlight the current challenges of gold nanozymes and look forward to attracting more attention for propelling the developments in this field.

The expression characteristic and prognostic role of Siglec-15 in lung adenocarcinoma.

Sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) has been identified as an immune suppressor and a promising candidate for immunotherapy of cancer management. However, the association between Siglec-15 expression and clinicopathological features of lung adenocarcinoma (LUAD), especially the prognostic role, is not fully elucidated. In this present study, a serial of bioinformatics analyses in both tissue and cell levels were conducted to provide an overview of Siglec-15 expression. Real-time quantitative PCR (qPCR) test, western blotting assay, and immunohistochemistry (IHC) analyses were conducted to evaluate the expression of Siglec-15 in LUAD. Survival analysis and Kaplan-Meier curve were employed to describe the prognostic parameters of LUAD. The results of bioinformatics analyses demonstrated the up-regulation of Siglec-15 expression in LUAD. The data of qPCR, western blotting, and IHC analyses further proved that the expression of Siglec-15 in LUAD tissues was significantly increased than that in noncancerous tissues. Moreover, the expression level of Siglec-15 protein in LUAD was substantially associated with TNM stage. LUAD cases with up-regulated Siglec-15 expression, positive N status, and advance TNM stage suffered a critical unfavorable prognosis. In conclusion, Siglec-15 could be identified as a novel prognostic biomarker in LUAD and targeting Siglec-15 may provide a promising strategy for LUAD immunotherapy.

Multimodal data integration for enhanced longitudinal prediction for cardiac and cerebrovascular events following initial diagnosis of obstructive sleep apnea syndrome.

Background: Obstructive sleep apnea syndrome (OSAS), a prevalent condition, often coexists with intricate metabolic issues and is frequently associated with negative cardiovascular outcomes. We developed a longitudinal prediction model integrating multimodal data for cardiovascular risk stratification of patients with an initial diagnosis of OSAS. Methods: We reviewed the data of patients with new-onset OSAS who underwent diagnostic polysomnography between 2018-19. Patients were treated using standard treatment regimens according to clinical practice guidelines. Results: Over a median follow-up of 32 months, 98/729 participants (13.4%) experienced our composite outcome. At a ratio of 7:3, cases were randomly divided into development (n = 510) and validation (n = 219) cohorts. A prediction nomogram was created using six clinical factors - sex, age, diabetes mellitus, history of coronary artery disease, triglyceride-glucose index, and apnea-hypopnea index. The prediction nomogram showed excellent discriminatory power, based on Harrell's C-index values of 0.826 (95% confidence interval (CI) = 0.779-0.873) for the development cohort and 0.877 (95% CI = 0.824-0.93) for the validation cohort. Moreover, comparing the predicted and observed major adverse cardiac and cerebrovascular events in both development and validation cohorts indicated that the prediction nomogram was well-calibrated. Decision curve analysis demonstrated the good clinical applicability of the prediction nomogram. Conclusions: Our findings demonstrated the construction of an innovative visualisation tool that utilises various types of data to predict poor outcomes in Chinese patients diagnosed with OSAS, providing accurate and personalised therapy. Registration: Chinese Clinical Trial Registry ChiCTR2300075727.