Epidemiology of Human Parainfluenza Virus Infections among Pediatric Patients in Hainan Island, China, 2021-2023.

Human parainfluenza viruses (HPIVs) are the leading causes of acute respiratory tract infections (ARTIs), particularly in children. During the COVID-19 pandemic, non-pharmaceutical interventions (NPIs) significantly influenced the epidemiology of respiratory viruses. This study analyzed 19,339 respiratory specimens from pediatric patients with ARTIs to detect HPIVs using PCR or tNGS, focusing on the period from 2021 to 2023. HPIVs were identified in 1395 patients (7.21%, 1395/19,339), with annual detection rates of 6.86% (303/4419) in 2021, 6.38% (331/5188) in 2022, and 7.82% (761/9732) in 2023. Notably, both the total number of tests and HPIV-positive cases increased in 2023 compared to 2021 and 2022. Seasonal analysis revealed a shift in HPIV prevalence from winter and spring in 2021-2022 to spring and summer in 2023. Most HPIV-positive cases were in children aged 0-7 years, with fewer infections among those aged 7-18 years. Since June 2022, HPIV-3 has been the most prevalent serotype (59.55%, 524/880), whereas HPIV-2 had the lowest proportion (0.80%, 7/880). The proportions of HPIV-1 (24.89%, 219/880) and HPIV-4 (15.45%, 136/880) were similar. Additionally, the incidence of co-infections with other common respiratory pathogens has increased since 2021. This study highlights rising HPIV detection rates post-COVID-19 and underscores the need for continuous surveillance of HPIVs to inform public health strategies for future epidemic seasons.

Sporolactobacillus-a new functional genus with potential applications.

Sporolactobacillus is a genus of lactic acid bacteria, which can be widely found in soil. According to NCBI, only 20 strains of the genus Sporolactobacillus have been identified through phenotypic and genotypic analysis, indicating their relatively low numbers compared to other lactic acid bacteria. Currently, there is a growing interest in isolating and studying Sporolactobacillus, particularly focusing on its physiological characteristics and conducting in vitro experiments. This paper provides a review of the sources and physiological characteristics of Sporolactobacillus, along with genotype analysis, carbohydrate metabolism traits, and potential antibacterial properties. It also delves into basic physiological characteristics, lactic acid production, and applications, offering insights for the future utilization of Sporolactobacillus and laying a foundation for exploring its potential applications.

Exploring Core fermentation microorganisms, flavor compounds, and metabolic pathways in fermented Rice and wheat foods.

The unique flavors of fermented foods significantly influence consumer purchasing choices, prompting widespread scientific interest in the flavor development process. Fermented rice and wheat foods are known for their unique flavors and they occupy an important place in the global diet. Many of these are produced on an industrial scale using starter cultures, whereas others rely on spontaneous fermentation, homemade production, or traditional activities. Microorganisms are key in shaping the sensory properties of fermented products through different metabolic pathways, thus earning the title "the essence of fermentation." Therefore, this study systematically summarizes the key microbial communities and their interactions that contribute positively to iconic fermented rice and wheat foods, such as steamed bread, bread, Mifen, and rice wine. This study revealed the mechanism by which these core microbial communities affect flavor and revealed the strategies of core microorganisms and related enzymes to enhance flavor during fermentation.

A Novel Amino Acid-Related Gene Signature Predicts Overall Survival in Patients With Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is an extremely harmful malignant tumor in the world. Since the energy metabolism and biosynthesis of HCC cells are closely related to amino acids, it is necessary to further explore the relationship between amino acid-related genes and the prognosis of HCC to achieve individualized treatment. We herein aimed to develop a prognostic model for HCC based on amino acid genes. METHODS: In this study, RNA-sequencing data of HCC patients were downloaded from the TCGA-LIHC cohort as the training cohort and the GSE14520 cohort as the validation cohort. Amino acid-related genes were derived from the Molecular Signatures Database. Univariate Cox and Lasso regression analysis were used to construct an amino acid-related signature (AARS). The predictive value of this risk score was evaluated by Kaplan-Meier (K-M) curve, receiver operating characteristic (ROC) curve, univariate and multivariate Cox regression analysis. Gene set variation analysis (GSVA) and immune characteristics evaluation were used to explore the underlying mechanisms. Finally, a nomogram was established to help the personalized prognosis assessment of patients with HCC. RESULTS: The AARS comprises 14 amino acid-related genes to predict overall survival (OS) in HCC patients. HCC patients were divided into AARS-high group and AARS-low group according to the AARS scores. The K-M curve, ROC curve, and univariate and multivariate Cox regression analysis verified the good prediction efficiency of the risk score. Using GSVA, we found that AARS variants were concentrated in four pathways, including cholesterol metabolism, delayed estrogen response, fatty acid metabolism, and myogenesis metabolism. CONCLUSION: Our results suggest that the AARS as a prognostic model based on amino acid-related genes is of great value in the prediction of survival of HCC, and can help improve the individualized treatment of patients with HCC.

Field-deployable viral diagnostic tools for dengue virus based on Cas13a and Cas12a.

The diagnosis of dengue virus (DENV) has been challenging particularly in areas far from clinical laboratories. Early diagnosis of pathogens is a prerequisite for the timely treatment and pathogen control. An ideal diagnostic for viral infections should possess high sensitivity, specificity, and flexibility. In this study, we implemented dual amplification involving Cas13a and Cas12a, enabling sensitive and visually aided diagnostics for the dengue virus. Cas13a recognized the target RNA by crRNA and formed the assembly of the Cas13a/crRNA/RNA ternary complex, engaged in collateral cleavage of nearby crRNA of Cas12a. The Cas12a/crRNA/dsDNA activator ternary complex could not be assembled due to the absence of crRNA of Cas12a. Moreover, the probe, with 5' and 3' termini labeled with FAM and biotin, could not be separated. The probes labeled with FAM and biotin, combined the Anti-FAM and the Anti-Biotin Ab-coated gold nanoparticle, and conformed sandwich structure on the T-line. The red line on the paper strip caused by clumping of AuNPs on the T-line indicated the detection of dengue virus. This technique, utilizing an activated Cas13a system cleaving the crRNA of Cas12a, triggered a cascade that amplifies the virus signal, achieving a low detection limit of 190 fM with fluorescence. Moreover, even at 1 pM, the red color on the T-line was easily visible by naked eyes. The developed strategy, incorporating cascade enzymatic amplification, exhibited good sensitivity and may serve as a field-deployable diagnostic tool for dengue virus.

Identification of potential biomarkers and pathways for asthenozoospermia by bioinformatics analysis and experiments.

Background: Asthenozoospermia, a type of male infertility, is primarily caused by dysfunctional sperm mitochondria. Despite previous bioinformatics analysis identifying potential key lncRNAs, miRNAs, hub genes, and pathways associated with asthenospermia, there is still a need to explore additional molecular mechanisms and potential biomarkers for this condition. Methods: We integrated data from Gene Expression Omnibus (GEO) (GSE22331, GSE34514, and GSE160749) and performed bioinformatics analysis to identify differentially expressed genes (DEGs) between normozoospermia and asthenozoospermia. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to gain insights into biological processes and signaling pathways. Weighted Gene Co-expression Network Analysis (WGCNA) identified gene modules associated with asthenozoospermia. Expression levels of key genes were assessed using datasets and experimental data. Gene Set Enrichment Analysis (GSEA) and correlation analysis identified pathways associated with the hub gene and explore the relationship between the ZNF764 and COQ9 and mitochondrial autophagy-related genes. Competitive endogenous RNA (ceRNA) networks were constructed, and in vitro experiments using exosome samples were conducted to validate this finding. Results: COQ9 was identified as a marker gene in asthenozoospermia, involved in autophagy, ATP-dependent chromatin remodeling, endocytosis, and cell cycle, etc. The ceRNA regulatory network (LINC00893/miR-125a-5p/COQ9) was constructed, and PCR demonstrated that LINC00893 and COQ9 were downregulated in asthenozoospermia, while miR-125a-5p and m6A methylation level of LINC00893 were upregulated in asthenozoospermia compared to normozoospermic individuals. Conclusion: The ceRNA regulatory network (LINC00893/miR-125a-5p/COQ9) likely plays a crucial role in the mechanism of asthenozoospermia. However, further functional experiments are needed to fully understand its significance.

Cross-feeding of bifidobacteria promotes intestinal homeostasis: a lifelong perspective on the host health.

Throughout the life span of a host, bifidobacteria have shown superior colonization and glycan abilities. Complex glycans, such as human milk oligosaccharides and plant glycans, that reach the colon are directly internalized by the transport system of bifidobacteria, cleaved into simple structures by extracellular glycosyl hydrolase, and transported to cells for fermentation. The glycan utilization of bifidobacteria introduces cross-feeding activities between bifidobacterial strains and other microbiota, which are influenced by host nutrition and regulate gut homeostasis. This review discusses bifidobacterial glycan utilization strategies, focusing on the cross-feeding involved in bifidobacteria and its potential health benefits. Furthermore, the impact of cross-feeding on the gut trophic niche of bifidobacteria and host health is also highlighted. This review provides novel insights into the interactions between microbe-microbe and host-microbe.

Circulation pattern and genetic variation of rhinovirus infection among hospitalized children on Hainan Island, before and after the dynamic zero-COVID policy, from 2021 to 2023.

Throughout the COVID-19 pandemic, rhinovirus (RV) remained notable persistence, maintaining its presence while other seasonal respiratory viruses were largely suppressed by pandemic restrictions during national lockdowns. This research explores the epidemiological dynamics of RV infections among pediatric populations on Hainan Island, China, specifically focusing on the impact before and after the zero-COVID policy was lifted. From January 2021 to December 2023, 19 680 samples were collected from pediatric patients hospitalized with acute lower respiratory tract infections (ARTIs) at the Hainan Maternal and Child Health Hospital. The infection of RV was detected by tNGS. RV species and subtypes were identified in 32 RV-positive samples representing diverse time points by analyzing the VP4/VP2 partial regions. Among the 19 680 pediatric inpatients with ARTIs analyzed, 21.55% were found to be positive for RV infection, with notable peaks observed in April 2021 and November 2022. A gradual annual decline in RV infections was observed, alongside a seasonal pattern of higher prevalence during the colder months. The highest proportion of RV infections was observed in the 0-1-year age group. Phylogenetic analysis on 32 samples indicated a trend from RV-A to RV-C in 2022. This observation suggests potential evolving dynamics within the RV species although further studies are needed due to the limited sample size. The research emphasizes the necessity for ongoing surveillance and targeted management, particularly for populations highly susceptible to severe illnesses caused by RV infections.

Neuronal pentraxin 2 correlates with neurodegeneration but not cognition in idiopathic normal pressure hydrocephalus (iNPH).

AIM OF THE STUDY: Neuronal pentraxin-2 (NPTX2) is a synaptic protein responsible for modulating plasticity at excitatory synapses. While the role of NPTX2 as a novel synaptic biomarker in cognitive disorders has been elucidated recently, its role in idiopathic normal pressure hydrocephalus (iNPH) is not yet understood. CLINICAL RATIONALE FOR STUDY: To determine if NPTX2 predicts cognition in patients with iNPH, and whether it could serve as a predictive marker for shunt outcomes. MATERIAL AND METHODS: 354 iNPH patients underwent cerebrospinal fluid drainage (CSF) as part of the tap test or extended lumbar drainage. Demographic and clinical measures including age, Evans Index (EI), Montreal Cognitive Assessment (MoCA) score, Functional Activities Questionnaire (FAQ) score, and baseline and post-shunt surgery Timed Up and Go (TUG) test scores were ascertained. CSF NPTX2 concentrations were measured using an ELISA. CSF ß-amyloid 1-40 (Aß1-40), ß-amyloid 1-42 (Aß1-42), and phosphorylated tau-181 (pTau-181) were measured by chemiluminescent assays. Spearman's correlation was used to determine the correlation between CSF NPTX2 concentrations and age, EI, MoCA and FAQ, TUG, Aß1-40/Aß1-42 ratio, and pTau-181 concentrations. Logistic regression was used to determine if CSF NPTX2 values were a predictor of short-term improvement post-CSF drainage or long-term improvement post-shunt surgery. RESULTS: There were 225 males and 129 females with a mean age of 77.7 years (± 7.06). Average CSF NPTX2 level in all iNPH patients was 559.97 pg/mL (± 432.87). CSF NPTX2 level in those selected for shunt surgery was 505.61 pg/mL (± 322.38). NPTX2 showed modest correlations with pTau-181 (r = 0.44, p < 0.001) with a trend for Aß42/Aß40 ratio (r = -0.1, p = 0.053). NPTX2 concentrations did not correlate with age (r = -0.012, p = 0.83) or MoCA score (r = 0.001, p = 0.87), but correlated negatively with FAQ (r = -0.15, p = 0.019). CONCLUSIONS: While CSF NPTX2 values correlate with neurodegeneration, they do not correlate with cognitive or functional measures in iNPH. CSF NPTX2 cannot serve as a predictor of either short-term or long-term improvement after CSF drainage. CLINICAL IMPLICATIONS: These results suggest that synaptic degeneration is not a core feature of iNPH pathophysiology.

Identification of functional genes in liver fibrosis based on bioinformatics analysis of a lncRNA-mediated ceRNA network.

BACKGROUND: Liver fibrosis is a major global healths problem; nevertheless, its molecular mechanism are not completely clear. This study aimed to build a lncRNA-miRNA-mRNA network, identify potentially related lncRNAs, and explore the pathogenesis of liver fibrosis. MATERIALS AND METHODS: We used the Gene Expression Omnibus databases and bioinformatics analysis to identify differentially expressed genes (DEGs) between liver fibrosis and normal tissues. The ceRNA network was constructed according to the interactions between DElncRNA, miRNA, and DEmRNA. Then, these DEGs were identified using functional enrichment analysis, and a protein-protein interaction (PPI) network was established. The critical lncRNAs were verified using the quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The ceRNA network was composed of three lncRNAs, five miRNAs, and 93 mRNAs. Gene Ontology functional enrichment analysis revealed significant enhancement in cell components, molecular function, and biological process. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed pathways associated with transcriptional misregulation in cancer, including the Rap1 signaling pathway, proteoglycans in cancer, mineral absorption, HTLV-l infection, and central carbon metabolism in cancer. According to the PPI network and the GSE84044 database, seven hub genes associated with liver fibrosis were identified. In addition, qRT-PCR revealed that lncRNA AC100861 (lncRNA TNFRSF10A-DT) was explicitly decreased in liver fibrosis tissues and activated hepatic stellate cells. CONCLUSIONS: In summary, this study preliminarily found that lncRNA TNFRSF10A-DT may be a biomarker for the diagnosis and outcome of liver fibrosis. We uncovered a novel lncRNA-mediated ceRNA regulatory mechanism in the pathogenesis of liver fibrosis.

Middle-aged and older people's preference for medical-elderly care integrated institutions in China: a discrete choice experiment study.

BACKGROUND: With the continuing impact of the aging population, medical-elderly care integrated institutions, as a way to bear the pressure of medical and elderly care, effectively ensure the quality of life of the elderly in their later years. OBJECTIVES: To explore the preferences of medical-elderly care integrated institutions among Chinese middle-aged and older people and to provide a reference for establishing elderly-oriented development of medical-elderly care integrated institutions. METHODS: In this study, a discrete choice experiment (DCE) was used to investigate the preferences of people aged 45 years and older in medical-elderly care integrated institutions in China from October 20, 2022, to November 10, 2022. A mixed logit regression model was used to analyze the DCE data. Participants' willingness to pay for each attribute was also calculated. RESULTS: Data from 420 participants who provided valid responses were included in the analysis. In terms of the choice preference, moderate service quality (vs. poor service quality: ß = 1.707, p < 0.001, 95% CI 1.343 ~ 2.071) and high medical technology level (vs. low medical technology level: ß = 1.535, p < 0.001, 95% CI 1.240 ~ 1.830) were the most important attributes to middle-aged and older people, followed by monthly cost, environmental facilities, the convenience of transportation, and entertainment activities. Regarding the willingness to pay, participants were more willing to pay for service quality and medical technology level than for other attributes. They were willing to pay $3156 and $2838 more for "poor service quality" and "low medical technology level," respectively, to receive "moderate service quality " (p = 0.007, 95% CI 963 ~ 5349) and "high medical technology level" (p = 0.005, 95% CI 852 ~ 4824). CONCLUSIONS: The state should attach great importance to the development of medical-elderly care integrated services industry, actively optimize the model of the medical-elderly care integrated service, improve the facilities, and create a healthy environment. At the same time, give full play to the role of medical insurance, long-term care insurance, and commercial insurance, so as to improve the comprehensive quality of life of the elderly. PUBLIC CONTRIBUTION: The design of the experimental selection was guided by 10 experts in the field, 5 Chinese government officials, and interviews and focus group discussions, without whose participation this study would not have been possible.

Exploring the regulatory role of Linc00893 in asthenozoospermia: Insights into sperm motility and SSC viability.

The role of long intergenic noncoding RNA 00893 (Linc00893) in asthenozoospermia (AS) and its impact on sperm motility remains unclear The present study explored the effect of Linc00893 on AS, specifically its effect on sperm motility and its relationship with spermatogonial stem cell (SSC) vitality and myosin heavy chain 9 (MYH9) protein expression. Linc00893 expression was analyzed in semen samples using reverse transcription­quantitative PCR, revealing a significant downregulation in samples from individuals with AS compared with those from healthy subjects. This downregulation was found to be negatively correlated with parameters of sperm motility. To further understand the role of Linc00893, small interfering RNA was used to knockdown its expression in SSCs. This knockdown led to a marked decrease in cell vitality and an increase in apoptosis. Notably, Linc00893 knockdown was shown to inhibit MYH9 expression by competitively binding with microRNA­107, a finding verified by dual­luciferase reporter and RNA immunoprecipitation assays. Furthermore, using the GSE160749 dataset from the Gene Expression Omnibus database, it was revealed that MYH9 protein expression was downregulated in AS samples. Subsequently, lentiviral vectors were constructed to induce overexpression of MYH9, which in turn reduced SSC apoptosis and counteracted the apoptosis triggered by Linc00893 knockdown. In conclusion, the present study identified the role of Linc00893 in AS, particularly its regulatory impact on sperm motility, SSC vitality and MYH9 expression. These findings may provide information on the potential regulatory mechanisms in AS development, and identify Linc00893 and MYH9 as possible targets for diagnosing and treating AS­related disorders.

Sleep and circadian rhythm disruption by NPTX2 loss of function.

Sleep and circadian rhythm disruption (SCRD) is commonly observed in aging, especially in individuals who experience progressive cognitive decline to mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, precise molecular mechanisms underlying the association between SCRD and aging are not fully understood. Orexin A is a well-characterized "sleep neuropeptide" that is expressed in hypothalamic neurons and evokes wake behavior. The importance of Orexin is exemplified in narcolepsy where it is profoundly down-regulated. Interestingly, the synaptic immediate early gene NPTX2 is co-expressed in Orexin neurons and is similarly reduced in narcolepsy. NPTX2 is also down-regulated in CSF of some cognitively normal older individuals and predicts the time of transition from normal cognition to MCI. The association between Orexin and NPTX2 is further evinced here where we observe that Orexin A and NPTX2 are highly correlated in CSF of cognitively normal aged individuals and raises the question of whether SCRD that are typically attributed to Orexin A loss of function may be modified by concomitant NPTX2 down-regulation. Is NPTX2 an effector of sleep or simply a reporter of orexin-dependent SCRD? To address this question, we examined NPTX2 KO mice and found they retain Orexin expression in the brain and so provide an opportunity to examine the specific contribution of NPTX2 to SCRD. Our results reveal that NPTX2 KO mice exhibit a disrupted circadian onset time, coupled with increased activity during the sleep phase, suggesting difficulties in maintaining states. Sleep EEG indicates distinct temporal allocation shifts across vigilance states, characterized by reduced wake and increased NREM time. Evident sleep fragmentation manifests through alterations of event occurrences during Wake and NREM, notably during light transition periods, in conjunction with an increased frequency of sleep transitions in NPTX2 KO mice, particularly between Wake and NREM. EEG spectral analysis indicated significant shifts in power across various frequency bands in the wake, NREM, and REM states, suggestive of disrupted neuronal synchronicity. An intriguing observation is the diminished occurrence of sleep spindles, one of the earliest measures of human sleep disruption, in NPTX2 KO mice. These findings highlight the effector role of NPTX2 loss of function as an instigator of SCRD and a potential mediator of sleep disruption in aging.

Corrigendum: Prevalence of iron-deficiency anemia in pregnant women with various thalassemia genotypes: thoughts on iron supplementation in pregnant women with thalassemia genes.

[This corrects the article DOI: 10.3389/fnut.2022.1005951.].

Identification of two novel papillomaviruses in belugas.

Introduction: Papillomaviruses (PVs) can cause hyperplasia in the skin and mucous membranes of humans, mammals, and non-mammalian animals, and are a significant risk factor for cervical and genital cancers. Methods: Using next-generation sequencing (NGS), we identified two novel strains of papillomavirus, PV-HMU-1 and PV-HMU-2, in swabs taken from belugas (Delphinapterus leucas) at Polar Ocean Parks in Qingdao and Dalian. Results: We amplified the complete genomes of both strains and screened ten belugas and one false killer whale (Pseudorca crassidens) for the late gene (L1) to determine the infection rate. In Qingdao, 50% of the two sampled belugas were infected with PV-HMU-1, while the false killer whale was negative. In Dalian, 71% of the eight sampled belugas were infected with PV-HMU-2. In their L1 genes, PV-HMU-1 and PV-HMU-2 showed 64.99 and 68.12% amino acid identity, respectively, with other members of Papillomaviridae. Phylogenetic analysis of combinatorial amino acid sequences revealed that PV-HMU-1 and PV-HMU-2 clustered with other known dolphin PVs but formed distinct branches. PVs carried by belugas were proposed as novel species under Firstpapillomavirinae. Conclusion: The discovery of these two novel PVs enhances our understanding of the genetic diversity of papillomaviruses and their impact on the beluga population.

Diversity and independent evolutionary profiling of rodent-borne viruses in Hainan, a tropical island of China.

The risk of emerging infectious diseases (EID) is increasing globally. More than 60% of EIDs worldwide are caused by animal-borne pathogens. This study aimed to characterize the virome, analyze the phylogenetic evolution, and determine the diversity of rodent-borne viruses in Hainan Province, China. We collected 682 anal and throat samples from rodents, combined them into 28 pools according to their species and location, and processed them for next-generation sequencing and bioinformatics analysis. The diverse viral contigs closely related to mammals were assigned to 22 viral families. Molecular clues of the important rodent-borne viruses were further identified by polymerase chain reaction for phylogenetic analysis and annotation of genetic characteristics such as arenavirus, coronavirus, astrovirus, pestivirus, parvovirus, and papillomavirus. We identified pestivirus and bocavirus in Leopoldoms edwardsi from Huangjinjiaoling, and bocavirus in Rattus andamanensis from the national nature reserves of Bangxi with low amino acid identity to known pathogens are proposed as the novel species, and their rodent hosts have not been previously reported to carry these viruses. These results expand our knowledge of viral classification and host range and suggest that there are highly diverse, undiscovered viruses that have evolved independently in their unique wildlife hosts in inaccessible areas.

The Hepatic Nerves Regulated Inflammatory Effect in the Process of Liver Injury: Is Nerve the Key Treating Target for Liver Inflammation?

Liver injury is a common pathological basis for various liver diseases. Chronic liver injury is often an important initiating factor in liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Currently, hepatitis A and E infections are the most common causes of acute liver injury worldwide, whereas drug toxicity (paracetamol overdose) in the USA and part of Western Europe. In recent years, chronic liver injury has become a common disease that harms human health. Meanwhile, the main causes of chronic liver injury are viral hepatitis (B, C) and long-term alcohol consumption worldwide. During the process of liver injury, massive inflammatory cytokines are stimulated by these hazardous factors, leading to a systemic inflammatory response syndrome, followed by a compensatory anti-inflammatory response, which causes immune cell dysfunction and sepsis, subsequent multi-organ failure. Cytokine release and immune cell infiltration-mediated aseptic inflammation are the most important features of the pathobiology of liver failure. From this perspective, diminishing the onset and progression of liver inflammation is of clinical importance in the treatment of liver injury. Although many studies have hinted at the critical role of nerves in regulating inflammation, there largely remains undetermined how hepatic nerves mediate immune inflammation and how the inflammatory factors released by these nerves are involved in the process of liver injury. Therefore, the purpose of this article is to summarize previous studies in the field related to hepatic nerve and inflammation as well as future perspectives on the aforementioned questions. Our findings were presented in three aspects: types of nerve distribution in the liver, how these nerves regulate immunity, and the role of liver nerves in hepatitis and liver failure.

NPTX2 in Cerebrospinal Fluid Predicts the Progression From Normal Cognition to Mild Cognitive Impairment.

OBJECTIVE: This study examined whether cerebrospinal fluid (CSF) baseline levels of the synaptic protein NPTX2 predict time to onset of symptoms of mild cognitive impairment (MCI), both alone and when accounting for traditional CSF Alzheimer's disease (AD) biomarker levels. Longitudinal NPTX2 levels were also examined. METHODS: CSF was collected longitudinally from 269 cognitively normal BIOCARD Study participants (mean baseline age = 57.7 years; mean follow-up = 16.3 years; n = 77 progressed to MCI/dementia). NPTX2 levels were measured from 3 correlated peptides using quantitative parallel reaction monitoring mass spectrometry. Levels of Aß42 /Aß40 , p-tau181 , and t-tau were measured from the same CSF specimens using Lumipulse automated electrochemiluminescence assays. RESULTS: In Cox regression models, lower baseline NPTX2 levels were associated with an earlier time to MCI symptom onset (hazard ratio [HR] = 0.76, SE = 0.09, p = 0.023). This association was significant for progression within 7 years (p = 0.036) and after 7 years from baseline (p = 0.001). Baseline NPTX2 levels improved prediction of time to MCI symptom onset after accounting for baseline AD biomarker levels (p < 0.01), and NPTX2 did not interact with the CSF AD biomarkers or APOE-ε4 genetic status. In linear mixed effects models, higher baseline p-tau181 and t-tau levels were associated with higher baseline levels of NPTX2 (both p < 0.001) and greater rates of NPTX2 declines over time. INTERPRETATION: NPTX2 may be a valuable prognostic biomarker during preclinical AD that provides additive and independent prediction of MCI onset among individuals who are cognitively normal. We hypothesize that NPTX2-mediated circuit homeostasis confers resilience during the early phase of AD. ANN NEUROL 2023;94:620-631.