Fine mapping and identification of candidate genes associated with powdery mildew resistance in melon (Cucumis melo L.).

Powdery mildew (PM), a common disease of many major crop species, including melon (Cucumis melo L.), affects plant growth and fruit quality and seriously reduces production. Using a combined morphological and molecular approach, we attribute the PM pathogen that naturally occurs in melon to Podosphaera xanthii, and specifically to physiological race 1. An investigation into the genetic basis of PM resistance in melon using the resistant accession 'PI 164637' and susceptible counterpart 'HDZ' reveals dominant inheritance of PM resistance at the seedling stage, supported by F2 and backcross population segregation ratios. Adult plant assessments indicate a major gene with an additive effect for PM resistance. Bulk segregant analysis coupled with high-throughput sequencing identified a significant quantitative trait locus on chromosome 6 that is associated with PM resistance. Genetic mapping narrowed down the candidate region to 63.5 kb using InDel molecular markers, harboring 12 candidate genes. The marker chr06_indel_5 047 127 demonstrated high accuracy in screening PM resistance in an F2 segregating population and 30 inbred lines as natural populations. Functional annotation and expression analysis of candidate genes revealed that MYB transcription factor MELO3C006700, GATA transcription factor MELO3C028829 and heparanase-like protein MELO3C006697 are promising candidate genes for PM resistance in melon. The genetic architecture underlying this resistance in melon offers valuable insights for breeding programs, and the identified markers, especially chr06_indel_5 047 127, may enable practical applications for marker-assisted selection in developing PM-resistant melon varieties.

The broad-spectrum deubiquitinating enzyme inhibitor PR-619 protects retinal ganglion cell and augments parkin-mediated mitophagy in experimental glaucoma.

Glaucoma is a leading cause of irreversible visual impairment worldwide, characterized by the progressive death of retinal ganglion cells (RGCs). Deubiquitinating enzyme (DUB) inhibitors have shown promise as pharmacological interventions for neurodegenerative disorders. Our study focuses on the pan-DUB inhibitor PR-619 and its potential neuroprotective effects on RGCs through modulation of parkin-mediated mitophagy in experimental glaucoma models. The results show that impaired mitophagy exists in RGCs of our experimental glaucomatous model. In vivo, PR-619 increased RGCs survival in glaucomatous rats. In vitro, it protected RGCs against excitotoxicity and reduced ubiquitin-specific protease (USP) 15 expression. Additionally, PR-619 upregulated parkin expression, increased LC3-II/LC3-I ratios, and elevated LAMP1 levels, indicating enhanced mitophagy in vivo and in vitro. Moreover, numbers of mitophagosomes were increased in optic nerves of PR-619-treated ocular hypertensive rats in vivo. Furthermore, parkin knockdown negated the salutary effects of PR-619 and attenuated expression of parkin-dependent mitophagy effectors in RGCs subjected to glutamate excitotoxicity in vitro. Collectively, these findings implicate augmented parkin-mediated mitophagy as the mechanistic substrate underscoring the neuroprotective capacity of PR-619 in experimental glaucoma. These revelations engender the prospect that pharmacological agents or biotherapeutics augmenting parkin-mediated mitophagy may proffer viable therapeutic modalities for glaucomatous neurodegeneration characterized by impaired mitophagy.

Role of mechanosensitive channel Piezo1 protein in intestinal inflammation regulation: A potential target.

The intestine is a hollow tract that primarily transports and digests food. It often encounters mechanical forces and exotic threats, resulting in increased intestinal inflammation attributed to the consistent threat of foreign pathogens. Piezo1, a mechanosensitive ion channel, is distributed broadly and abundantly in the intestinal tissue. It transduces mechanical signals into electrochemical signals and participates in many critical life activities, such as proliferation, differentiation, cell apoptosis, immune cell activation, and migration. Its effect on inflammation has been discussed in detail in systems, such as musculoskeletal (osteoarthritis) and cardiac (myocarditis), but the effects on intestinal inflammation remain unelucidated. Piezo1 regulates mucosal layer and epithelial barrier homeostasis during the complex intestinal handling of foreign antigens and tissue trauma. It initiates and spreads immune responses and causes distant effects of inflammation in the vascular and lymphatic systems, but reports of the effects of Piezo1 in intestinal inflammation are scarce. Therefore, this study aimed to discuss the role of Piezo1 in intestinal inflammation and explore novel therapeutic targets.

Cancer immunotherapy and its facilitation by nanomedicine.

Cancer immunotherapy has sparked a wave of cancer research, driven by recent successful proof-of-concept clinical trials. However, barriers are emerging during its rapid development, including broad adverse effects, a lack of reliable biomarkers, tumor relapses, and drug resistance. Integration of nanomedicine may ameliorate current cancer immunotherapy. Ultra-large surface-to-volume ratio, extremely small size, and easy modification surface of nanoparticles enable them to selectively detect cells and kill cancer cells in vivo. Exciting synergistic applications of the two approaches have emerged in treating various cancers at the intersection of cancer immunotherapy and cancer nanomedicine, indicating the potential that the combination of these two therapeutic modalities can lead to new paradigms in the treatment of cancer. This review discusses the status of current immunotherapy and explores the possible opportunities that the nanomedicine platform can make cancer immunotherapy more powerful and precise by synergizing the two approaches.

Prevalence, incidence, and case fatality of tuberculous meningitis in adults living with HIV: a systematic review and meta-analysis.

BACKGROUND: Tuberculous meningitis (TBM) emerges as a grave complication of tuberculosis in people living with HIV (PLWH). The diagnosis and treatment of TBM pose significant challenges, leading to elevated mortality rates. To comprehensively grasp the epidemiological landscape of TBM in PLWH, a systematic review and meta-analysis were meticulously undertaken. METHODS: We performed a comprehensive search in PubMed, Embase, and Web of Science from database inception to September 19th, 2023, with no limitations on the publication type. The search terms were HIV/AIDS terms (AIDS OR HIV OR PLWH) and TBM-related terms (tuberculous meningitis OR TBM). Studies included in this meta-analysis evaluated the incidence of TBM among PLWH, or we were able to calculate the incidence of TBM among PLWH from the research. RESULTS: The analysis revealed that the prevalence of TBM among PLWH was 13.6% (95% CI: 6.6-25.9%), with an incidence rate of 1.5 cases per 1000 persons per year. The case fatality rate was found to be 38.1% (95% CI: 24.3-54.1%). No significant publication bias was observed. Meta-regression analysis identified the proportion of females and finance situation as factors influencing the outcomes. CONCLUSIONS: Our study highlights TBM as a prevalent opportunistic infection that targets the central nervous system in PLWH. The elevated case fatality rate is especially prominent among PLWH in impoverished regions, underscores the pressing necessity for enhanced management strategies for PLWH suffering from TBM. TRIAL REGISTRATION: PROSPERO; No: CRD42022338586.

Evidence that spatial scale and environment factors explain grassland community assembly in woodland-grassland ecotones.

How communities of living organisms assemble has long been a central question in ecology. The impact of habitat filtering and limiting similarity on plant community structures is well known, as both processes are influenced by individual responses to environmental fluctuations. Yet, the precise identifications and quantifications of the potential abiotic and biotic factors that shape community structures at a fine scale remains a challenge. Here, we applied null model approaches to assess the importance of habitat filtering and limiting similarity at two spatial scales. We used 63 natural vegetation plots, each measuring 5 × 5 m, with three nested subplots measuring 1 × 1 m, from the 2021 field survey, to examine the alpha diversity as well as beta diversity of plots and subplots. Linear mixed-effects models were employed to determine the impact of environmental variables on assembly rules. Our results demonstrate that habitat filtering is the dominant assembly rules at both the plot and subplot levels, although limiting similarity assumes stronger at the subplot level. Plot-level limiting similarity exhibited a positive association with fine-scale partitioning, suggesting that trait divergence originated from a combination of limiting similarity and spatial partitioning. Our findings also reveal that the community assembly varies more strongly with the mean annual temperature gradient than the mean annual precipitation. This investigation provides a pertinent illustration of non-random assembly rules from spatial scale and environmental factors in plant communities in the loess hilly region. It underscores the critical influence of spatial and environmental constraints in understanding the assembly of plant communities.

Hybrid nanoflower-based electrochemical lateral flow immunoassay for Escherichia coli O157 detection.

An electrochemical biosensor has been developed for detection of Escherichia coli O157 by integrating lateral flow with screen-printed electrodes. The screen-printed electrodes were attached under the lateral flow detection line, and organic-inorganic nanoflowers prepared from E. coli O157-specific antibodies as an organic component were attached to the lateral flow detection line. In the presence of E. coli O157, an organic-inorganic nanoflower-E. coli O157-antimicrobial peptide-labelled ferrocene sandwich structure is formed on the lateral flow detection line. Differential pulse voltammetry is applied using a smartphone-based device to monitor ferrocene on the detection line. The resulting electrochemical biosensor could specifically detect E. coli O157 with a limit of detection of 25 colony-forming units mL-1. Through substitution of antibodies of organic components in organic-inorganic nanoflowers, biosensors have great potential for the detection of other pathogens in biomedical research and clinical diagnosis.

Dysregulation of Gut Microbiota-Derived Neuromodulatory Amino Acid Metabolism in Human Immunodeficiency Virus-Associated Neurocognitive Disorder: An Integrative Metagenomic and Metabolomic Analysis.

OBJECTIVE: Although accumulating evidence implicating altered gut microbiota in human immunodeficiency virus (HIV) infection and neurodegenerative disorders; however, the association between dysbiosis of the gut microbiota and metabolites in the pathogenesis of HIV-associated neurocognitive disorder (HAND) remains unclear. METHODS: Fecal and plasma samples were obtained from 3 cohorts (HAND, HIV-non-HAND, and healthy controls), metagenomic analysis and metabolomic profiling were performed to investigate alterations in the gut microbial composition and circulating metabolites in HAND. RESULTS: The gut microbiota of people living with HIV (PLWH) had an increased relative abundance of Prevotella and a decreased relative abundance of Bacteroides. In contrast, Prevotella and Megamonas were substantially decreased, and Bacteroides and Phocaeicola were increased in HAND patients. Moreover, untargeted metabolomics identified several neurotransmitters and certain amino acids associated with neuromodulation, and the differential metabolic pathways of amino acids associated with neurocognition were depleted in HAND patients. Notably, most neuromodulatory metabolites are associated with an altered abundance of specific gut bacteria. INTERPRETATION: Our findings provide new insights into the intricate interplay between the gut and microbiome-brain axis in the pathogenesis of HAND, highlighting the potential for developing novel therapeutic strategies that specifically target the gut microbiota. ANN NEUROL 2024;96:306-320.

A sensitive fluorescence biosensor based on ligation-transcription and CRISPR/Cas13a-assisted cascade amplification strategies to detect the H1N1 virus.

We propose a sensitive H1N1 virus fluorescence biosensor based on ligation-transcription and CRISPR/Cas13a-assisted cascade amplification strategies. Products are generated via the hybridization of single-stranded DNA (ssDNA) probes containing T7 promoter and crRNA templates to a target RNA sequence using SplintR ligase. This generates large crRNA quantities in the presence of T7 RNA polymerase. At such crRNA quantities, ternary Cas13a, crRNA, and activator complexes are successfully constructed and activate Cas13a to enhance fluorescence signal outputs. The biosensor sensitively and specifically monitored H1N1 viral RNA levels down to 3.23 pM and showed good linearity when H1N1 RNA concentrations were 100 pM-1 µM. Biosensor specificity was also excellent. Importantly, our biosensor may be used to detect other viral RNAs by altering the sequences of the two probe junctions, with potential applications for the clinical diagnosis of viruses and other biomedical studies.

Insecticidal Activity of Essential Oils and Their Synergistic Effect on Improving the Efficacy of ß-Cypermethrin against Blattella germanica.

We screened the contact activity of 32 commercial essential oils (EOs) and their synergistic effect with ß-cypermethrin against Blattella germanica. Results showed that the most effective EOs against B. germanica were from Illicium verum, Syzygium aromaticum, and Cinnamomum camphora, with LD50 values of less than 500 µg/insect. The most potent synergistic effects of ß-cypermethrin on B. germanica were from Dysphania ambrosioides and Mentha canadensis. Both oils have a co-toxic factor of 133.33. The results of the major compound testing of the EOs showed that trans-anisaldehyde and thymol have the best insecticidal activity against B. germanica, with LD50 values of 141.30 and 138.61 µg/insect, respectively. The compounds with the best synergistic effect on ß-cypermethrin were γ-terpinene and linalool at a concentration of 0.5%. The co-toxic factors for γ-terpinene and linalool were 150 and 133.33, respectively, which were similar to the synergistic effect observed with 2% piperonyl butoxide.

gp120-derived amyloidogenic peptides form amyloid fibrils that increase HIV-1 infectivity.

Apart from mediating viral entry, the function of the free HIV-1 envelope protein (gp120) has yet to be elucidated. Our group previously showed that EP2 derived from one ß-strand in gp120 can form amyloid fibrils that increase HIV-1 infectivity. Importantly, gp120 contains ~30 ß-strands. We examined whether gp120 might serve as a precursor protein for the proteolytic release of amyloidogenic fragments that form amyloid fibrils, thereby promoting viral infection. Peptide array scanning, enzyme degradation assays, and viral infection experiments in vitro confirmed that many ß-stranded peptides derived from gp120 can indeed form amyloid fibrils that increase HIV-1 infectivity. These gp120-derived amyloidogenic peptides, or GAPs, which were confirmed to form amyloid fibrils, were termed gp120-derived enhancers of viral infection (GEVIs). GEVIs specifically capture HIV-1 virions and promote their attachment to target cells, thereby increasing HIV-1 infectivity. Different GAPs can cross-interact to form heterogeneous fibrils that retain the ability to increase HIV-1 infectivity. GEVIs even suppressed the antiviral activity of a panel of antiretroviral agents. Notably, endogenous GAPs and GEVIs were found in the lymphatic fluid, lymph nodes, and cerebrospinal fluid (CSF) of AIDS patients in vivo. Overall, gp120-derived amyloid fibrils might play a crucial role in the process of HIV-1 infectivity and thus represent novel targets for anti-HIV therapeutics.

Probing Hyperbolic Shear Polaritons in ß-Ga2O3 Nanostructures Using STEM-EELS.

Phonon polaritons, quasiparticles arising from strong coupling between electromagnetic waves and optical phonons, have potential for applications in subdiffraction imaging, sensing, thermal conduction enhancement, and spectroscopy signal enhancement. A new class of phonon polaritons in low-symmetry monoclinic crystals, hyperbolic shear polaritons (HShPs), have been verified recently in ß-Ga2O3 by free electron laser (FEL) measurements. However, detailed behaviors of HShPs in ß-Ga2O3 nanostructures still remain unknown. Here, by using monochromatic electron energy loss spectroscopy in conjunction with scanning transmission electron microscopy, the experimental observation of multiple HShPs in ß-Ga2O3 in the mid-infrared (MIR) and far-infrared (FIR) ranges is reported. HShPs in various ß-Ga2O3 nanorods and a ß-Ga2O3 nanodisk are excited. The frequency-dependent rotation and shear effect of HShPs reflect on the distribution of EELS signals. The propagation and reflection of HShPs in nanostructures are clarified by simulations of electric field distribution. These findings suggest that, with its tunable broad spectral HShPs, ß-Ga2O3 is an excellent candidate for nanophotonic applications.

Beyond pathways: Accelerated flavonoids candidate identification and novel exploration of enzymatic properties using combined mapping populations of wheat.

Although forward-genetics-metabolomics methods such as mGWAS and mQTL have proven effective in providing myriad loci affecting metabolite contents, they are somehow constrained by their respective constitutional flaws such as the hidden population structure for GWAS and insufficient recombinant rate for QTL. Here, the combination of mGWAS and mQTL was performed, conveying an improved statistical power to investigate the flavonoid pathways in common wheat. A total of 941 and 289 loci were, respectively, generated from mGWAS and mQTL, within which 13 of them were co-mapped using both approaches. Subsequently, the mGWAS or mQTL outputs alone and their combination were, respectively, utilized to delineate the metabolic routes. Using this approach, we identified two MYB transcription factor encoding genes and five structural genes, and the flavonoid pathway in wheat was accordingly updated. Moreover, we have discovered some rare-activity-exhibiting flavonoid glycosyl- and methyl-transferases, which may possess unique biological significance, and harnessing these novel catalytic capabilities provides potentially new breeding directions. Collectively, we propose our survey illustrates that the forward-genetics-metabolomics approaches including multiple populations with high density markers could be more frequently applied for delineating metabolic pathways in common wheat, which will ultimately contribute to metabolomics-assisted wheat crop improvement.

Identification and Validation of a Prognostic Signature Derived from the Cancer Stem Cells for Oral Squamous Cell Carcinoma.

The progression and metastasis of oral squamous cell carcinoma (OSCC) are highly influenced by cancer stem cells (CSCs) due to their unique self-renewal and plasticity. In this study, data were obtained from a single-cell RNA-sequencing dataset (GSE172577) in the GEO database, and LASSO-Cox regression analysis was performed on 1344 CSCs-related genes to establish a six-gene prognostic signature (6-GPS) consisting of ADM, POLR1D, PTGR1, RPL35A, PGK1, and P4HA1. High-risk scores were significantly associated with unfavorable survival outcomes, and these features were thoroughly validated in the ICGC. The results of nomograms, calibration plots, and ROC curves confirmed the good prognostic accuracy of 6-GPS for OSCC. Additionally, the knockdown of ADM or POLR1D genes may significantly inhibit the proliferation, migration, and invasion of OSCC cells through the JAK/HIF-1 pathway. Furthermore, cell-cycle arrest occurred in the G1 phase by suppressing Cyclin D1. In summary, 6-GPS may play a crucial role in the occurrence and development of OSCC and has the potential to be developed further as a diagnostic, therapeutic, and prognostic tool for OSCC.

Crosstalk between gut microbiome and neuroinflammation in pathogenesis of HIV-associated neurocognitive disorder.

HIV-associated neurocognitive disorder (HAND) has become a chronic neurodegenerative disease affecting the quality of life in people living with HIV (PLWH). Despite an established association between HAND and neuroinflammation induced by HIV proteins (gp120, Tat, Rev., Nef, and Vpr), the pathogenesis of HAND remains to be fully elucidated. Accumulating evidence demonstrated that the gut microbiome is emerging as a critical regulator of various neurodegenerative diseases (e.g., Parkinson's disease, Alzheimer's disease), suggesting that the crosstalk between the gut microbiome and neuroinflammation may contribute to the development of these diseases, for example, gut dysbiosis and microbiota-derived metabolites can trigger inflammation in the brain. However, the potential role of the gut microbiome in the pathogenesis of HAND remains largely unexplored. In this review, we aim to discuss and elucidate the HAND pathogenesis correlated with gut microbiome and neuroinflammation, and intend to explore the probable intervention strategies for HAND.

Hygroscopic Solutes Enable Non-van der Waals Electrolytes for Fire-Tolerant Dual-Air Batteries.

Thermal safety issues of batteries have hindered their large-scale applications. Nonflammable electrolytes improved safety but solvent evaporation above 100 °C limited thermal tolerance, lacking reliability. Herein, fire-tolerant metal-air batteries were realized by introducing solute-in-air electrolytes whose hygroscopic solutes could spontaneously reabsorb the evaporated water solvent. Using Zn/CaCl2 -in-air/carbon batteries as a proof-of-concept, they failed upon burning at 631.8 °C but self-recovered then by reabsorbing water from the air at room temperature. Different from conventional aqueous electrolytes whose irreversible thermal transformation is determined by the boiling points of solvents, solute-in-air electrolytes make this transformation determined by the much higher decomposition temperature of solutes. It was found that stronger intramolecular bonds instead of intermolecular (van der Waals) interactions were strongly correlated to ultra-high tolerance temperatures of our solute-in-air electrolytes, inspiring a concept of non-van der Waals electrolytes. Our study would improve the understanding of the thermal properties of electrolytes, guide the design of solute-in-air electrolytes, and enhance battery safety.

Deshielding Anions Enable Solvation Chemistry Control of LiPF6-Based Electrolyte toward Low-Temperature Lithium-Ion Batteries.

Severe capacity decay under subzero temperatures remains a significant challenge for lithium-ion batteries (LIBs) due to the sluggish interfacial kinetics. Current efforts to mitigate this deteriorating interfacial behavior rely on high-solubility lithium salts (e.g., Lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), Lithium bis(fluorosulfonyl)imide (LiFSI))-based electrolytes to construct anion participated solvation structures. However, such electrolytes bring issues of corrosion on the current collector and increased costs. Herein, the most commonly used Lithium hexafluorophosphate (LiPF6) instead, to establish a peculiar solvation structure with a high ratio of ion pairs and aggregates by introducing a deshielding NO3 - additive for low-temperature LIBs is utilized. The deshielding anion significantly reduces the energy barrier for interfacial behavior at low temperatures. Benefiting from this, the graphite (Gr) anode retains a high capacity of ≈72.3% at -20 °C, which is far superior to the 32.3% and 19.4% capacity retention of counterpart electrolytes. Moreover, the LiCoO2/Gr full cell exhibits a stable cycling performance of 100 cycles at -20 °C due to the inhibited lithium plating. This work heralds a new paradigm in LiPF6-based electrolyte design for LIBs operating at subzero temperatures.

Boosting Solid-State Reconversion Reactivity to Mitigate Lithium Trapping for High Initial Coulombic Efficiency.

An initial Coulombic efficiency (ICE) higher than 90% is crucial for industrial lithium-ion batteries, but numerous electrode materials are not standards compliant. Lithium trapping, due to i) incomplete solid-state reaction of Li+ generation and ii) sluggish Li+ diffusion, undermines ICE in high-capacity electrodes (e.g., conversion-type electrodes). Current approaches mitigating lithium trapping emphasize ii) nanoscaling (<50 nm) to minimize Li+ diffusion distance, followed by severe solid electrolyte interphase formation and inferior volumetric energy density. Herein, this work accentuates i) instead, to demonstrate that the lithium trapping can be mitigated by boosting the solid-state reaction reactivity. As a proof-of-concept, ternary LiFeO2 anodes, whose discharged products contain highly reactive vacancy-rich Fe nanoparticles, can alleviate lithium trapping and enable a remarkable average ICE of ≈92.77%, much higher than binary Fe2 O3 anodes (≈75.19%). Synchrotron-based techniques and theoretical simulations reveal that the solid-state reconversion reaction for Li+ generation between Fe and Li2 O can be effectively promoted by the Fe-vacancy-rich local chemical environment. The superior ICE is further demonstrated by assembled pouch cells. This work proposes a novel paradigm of regulating intrinsic solid-state chemistry to ameliorate electrochemical performance and facilitate industrial applications of various advanced electrode materials.

Effects of SARS-CoV-2 infection on hypothyroidism and subclinical hypothyroidism: a meta-analysis.

Background: In recent years, the outbreak of COVID-19 caused by SARS-CoV-2 has been witnessed globally. However, the impact of SARS-CoV-2 infection on thyroid dysfunction and subclinical thyroid dysfunction remains unclear. Therefore, this meta-analysis aimed to assess the effects of SARS-CoV-2 infection on thyroid dysfunction and its relationship with the severity of COVID-19. Methods: We systematically searched databases including PubMed, Willey Library, Embase, Web of Science, CNKI, Wanfang, and VIP. We focused on randomized controlled trials, case-control studies, and cohort studies published between December 2019 and August 2023, examining the association between SARS-CoV-2 infection and hypothyroidism, with a specific emphasis on the severity of the infection. The quality of the research was assessed using the Newcastle-Ottawa Scale (NOS), while statistical analysis was conducted using the meta and metafor packages in R 4.2.1 software. Results: For the meta-analysis, a total of eight articles were identified based on strict inclusion and exclusion criteria. For the association between SARS-CoV-2 infection and hypothyroidism, three studies (266 samples) comparing TSH levels of COVID-19 and control groups showed no difference in TSH levels [SMD=-0.04,95%CI(-1.22,1.15),P=0.95]. Additionally, two studies examining TT3 (a sample of 176 cases) and two studies examining TT4 (a sample of 176 cases) also showed no difference in TT3 and TT4 between the COVID-19 group and the control group, respectively. However, when evaluating the severity of COVID-19, six studies (565 samples) showed that TSH in the severe group was significantly lower than in the mild group [SMD = -0.55, 95% CI (-0.96, -0.14)], while FT3 was also lower in the severe group [SMD = -0.96, 95% CI (-1.24, -0.67)]. No noticeable differences were observed between the severe and mild groups in their TT3, FT4, and TT4 levels. Conclusion: SARS-CoV-2 infection may have detrimental effects on thyroid function in individuals with severe symptoms. More research is needed to confirm and explore this relationship. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023486042.

New insights into intestinal macrophages in necrotizing enterocolitis: the multi-functional role and promising therapeutic application.

Necrotizing enterocolitis (NEC) is an inflammatory intestinal disease that profoundly affects preterm infants. Currently, the pathogenesis of NEC remains controversial, resulting in limited treatment strategies. The preterm infants are thought to be susceptible to gut inflammatory disorders because of their immature immune system. In early life, intestinal macrophages (IMφs), crucial components of innate immunity, demonstrate functional plasticity and diversity in intestinal development, resistance to pathogens, maintenance of the intestinal barrier, and regulation of gut microbiota. When the stimulations of environmental, dietary, and bacterial factors interrupt the homeostatic processes of IMφs, they will lead to intestinal disease, such as NEC. This review focuses on the IMφs related pathogenesis in NEC, discusses the multi-functional roles and relevant molecular mechanisms of IMφs in preterm infants, and explores promising therapeutic application for NEC.