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Respiratory fungal infection is a severe clinical problem, especially in patients with compromised immune functions. , and endemic fungi are major pulmonary fungal pathogens that are able to result in life-threatening invasive diseases. Growing data being reported have indicated that multiple cells and molecules orchestrate the host's response to a fungal infection in the lung. Upon fungal challenge, innate myeloid cells including macrophages, dendritic cells (DC), and recruited neutrophils establish the first line of defense through the phagocytosis and secretion of cytokines. Natural killer cells control the fungal expansion in the lung via the direct and indirect killing of invading organisms. Adaptive immune cells including Th1 and Th17 cells confer anti-fungal activity by producing their signature cytokines, interferon-γ, and IL-17. In addition, lung epithelial cells (LEC) also participate in the resistance against fungal infection by internalization, inflammatory cytokine production, or antimicrobial peptide secretion. In the host cells mentioned above, various molecules with distinct functions modulate the immune defense signaling: Pattern recognition receptors (PRRs) such as dectin-1 expressed on the cell surface are involved in fungal recognition; adaptor proteins such as MyD88 and TRAF6 are required for transduction of signals to the nucleus for transcriptional regulation; inflammasomes also play crucial roles in the host's defense against a fungal infection in the lung. Furthermore, transcriptional factors modulate the transcriptions of a series of genes, especially those encoding cytokines and chemokines, which are predominant regulators in the infectious microenvironment, mediating the cellular and molecular immune responses against a fungal infection in the lung.

Bronchiolitis obliterans (BO) is a disease characterized by airway obstruction and fibrosis that can occur in all age groups. Bronchiolitis obliterans syndrome (BOS) is a clinical manifestation of BO in patients who have undergone lung transplantation or hematopoietic stem cell transplantation. Persistent inflammation and fibrosis of small airways make the disease irreversible, eventually leading to lung failure. The pathogenesis of BO is not entirely clear, but immune disorders are commonly involved, with various immune cells playing complex roles in different BO subtypes. Accordingly, the US Food and Drug Administration (FDA) has recently approved several new drugs that can alleviate chronic graft-versus-host disease (cGVHD) by regulating the function of immune cells, some of which have efficacy specifically with cGVHD-BOS. In this review, we will discuss the roles of different immune cells in BO/BOS, and introduce the latest drugs targeting various immune cells as the main target. This study emphasizes that immune dysfunction is an important driving factor in its pathophysiology. A better understanding of the role of the immune system in BO will enable the development of targeted immunotherapies to effectively delay or even reverse this condition.

MicroRNAs (miRNAs) are indispensable regulators for development and defense in eukaryotes. However, the miRNA species have not been explored for rice (Oryza sativa) immunity against the blast fungus Magnaporthe oryzae, the most devastating fungal pathogen in rice production worldwide. Here, by deep sequencing small RNA libraries from susceptible and resistant lines in normal conditions and upon M. oryzae infection, we identified a group of known rice miRNAs that were differentially expressed upon M. oryzae infection. They were further classified into three classes based on their expression patterns in the susceptible japonica line Lijiangxin Tuan Hegu and in the resistant line International Rice Blast Line Pyricularia-Kanto51-m-Tsuyuake that contains a single resistance gene locus, Pyricularia-Kanto 51-m (Pikm), within the Lijiangxin Tuan Hegu background. RNA-blot assay of nine of them confirmed sequencing results. Real-time reverse transcription-polymerase chain reaction assay showed that the expression of some target genes was negatively correlated with the expression of miRNAs. Moreover, transgenic rice plants overexpressing miR160a and miR398b displayed enhanced resistance to M. oryzae, as demonstrated by decreased fungal growth, increased hydrogen peroxide accumulation at the infection site, and up-regulated expression of defense-related genes. Taken together, our data indicate that miRNAs are involved in rice immunity against M. oryzae and that overexpression of miR160a or miR398b can enhance rice resistance to the disease.

Inflammatory bowel disease (IBD) is a chronic, recurrent gastrointestinal inflammation that affects millions of people around the world. Loganin, an iridoid glycoside, has shown the anti‐inflammatory effects. However, the effect of loganin on IBD and its underlying molecular mechanism are not clear. The present study aimed to investigate whether loganin could alleviate IBD and its mechanisms. The intestinal epithelial Caco‐2 cell line was treated with lipopolysaccharide (LPS) to establish an in vitro IBD model. MTT assay was used to detect cell viability. The expression and release level of inflammatory factors were determined by both real‐time‐PCR and ELISA. Western blotting was used to assess the NF‐κB and JAK/STAT3 pathway‐related protein levels. The results showed that loganin repressed the expression and release of IL‐6, TNF‐α, and IL‐1β, and inhibited TLR4/NF‐κB and JAK/STAT3 signaling pathways in a concentration‐dependent manner. Overexpression of TLR4 could reverse the effect of loganin, leading to activation of NF‐κB signaling and production of inflammatory factors. Meanwhile, IGF‐1, a JAK/STAT3 signaling activator, could also reverse the anti‐inflammation effect of loganin. In conclusion, loganin inhibited LPS‐activated intestinal epithelial inflammation by repressing TLR4/NF‐κB and JAK/STAT3 signaling pathway.

( ) infections in children can occur secondary to inborn errors of immunity (IEIs). We aimed to investigate the clinical and genetic features of infection in Chinese pediatric patients. We retrospectively reviewed 18 pediatric patients with IEIs who were diagnosed with infections at five public hospitals in China from January 2015 to January 2023. The common clinical features among the patients were fever, cough, and hepatomegaly. The most common severe complications included septic shock, hemophagocytic lymphohistiocytosis (HLH), and acute respiratory distress syndrome (ARDS). Three cases presented with pan-hypogammaglobulinemia, while three other cases showed heightened levels of IgM. Elevated levels of IgE were detected in five cases, and six cases exhibited decreased T lymphocyte absolute counts. Four children were diagnosed with hyperimmunoglobulin M syndrome (HIGM) due to mutations, three cases had severe combined immunodeficiency (SCID), and five were diagnosed with hyper-IgE syndrome (HIES). Gain-of-function (GOF) mutations in led to STAT1 GOF in four cases. One patient was diagnosed with caspase-recruitment domain (CARD9) deficiency due to a compound mutation in the gene, while another patient was confirmed with adenosine deaminase (ADA) deficiency. infections in children with IEIs induced severe systemic complications. These children commonly exhibited abnormal immunoglobulin levels in peripheral blood, and underlying IEIs associated with infections have enhanced our understanding of the disease.

Aflatoxins, widely found in feed and foodstuffs, are potentially harmful to human and animal health because of their high toxicity. In this study, a strain of Bacillus amyloliquefaciens B10 with a strong ability to degrade aflatoxin B1 (AFB1) was screened; it could degrade 2.5 μg/mL of AFB1 within 96 h. The active substances of Bacillus amyloliquefaciens B10 for the degradation of AFB1 mainly existed in the culture supernatant. A new laccase with AFB1-degrading activity was separated by ammonium sulfate precipitation, diethylaminoethyl (DEAE) and gel filtration chromatography. The results of molecular docking showed that B10 laccase and aflatoxin had a high docking score. The coding sequence of the laccase was successfully amplified from cDNA by PCR and cloned into E. coli. The purified laccase could degrade 79.3% of AFB1 within 36 h. The optimum temperature for AFB1 degradation was 40 °C, and the optimum pH was 6.0–8.0. Notably, Mg2+ and dimethyl sulfoxide (DMSO) could enhance the AFB1-degrading activity of B10 laccase. Mutation of the three key metal combined sites of B10 laccase resulted in the loss of AFB1-degrading activity, indicating that these three metal combined sites of B10 laccase play an essential role in the catalytic degradation of AFB1.

Background and aims Early diagnosis of biliary atresia (BA), particularly distinguishing it from other causes of neonatal cholestasis (NC), is challenging. This study aimed to design and validate a predictive model for BA by using the data available at the initial presentation. Methods Infants presenting with NC were retrospectively identified from tertiary referral hospitals and constituted the model design cohort ( n  = 148); others were enrolled in a prospective observational study and constituted the validation cohort ( n  = 21). Clinical, laboratory, and abdominal ultrasonographic features associated with BA were assessed. A prediction model was developed using logistic regression and decision tree (DT) analyses. Results Three predictors, namely, gamma glutamyl transpeptidase (γGT) level, triangular cord sign (TC sign), and gallbladder abnormalities, were identified as factors for diagnosing BA in multivariate logistic regression, which was used to develop the DT model. The area under the receiver operating characteristic (ROC) curve (AUC) value for the model was 0.905, which was greater than those for γGT level, TC sign, or gallbladder abnormalities alone in the prediction of BA. Conclusion A simple prediction model combining liver function and abdominal ultrasonography findings can provide a moderate and early estimate of the risk of BA in patients with NC.

Background Helicobacter pylori ( H. pylori ) infection is associated with remodeling of gut microbiota. Many studies have found H. pylori infection and eradication therapy can alter the gut microbiota. However, few studies explored the impact of eradication therapy containing minocycline and metronidazole on gut microbiota. Aim The objective of the present study was to explore the changes of gut microbiota after H. pylori infection. Besides, learn more about the dynamic changes of gut microbiota during different stages of eradication treatment containing minocycline, metronidazole, bismuth agents and proton pump inhibitors. Methods Sixty stool samples from the patients with H. pylori infection before eradication, 14 and 42 days after eradication, and ten stool samples from non-infected individuals were collected. Subsequently, we performed 16S rRNA gene amplicon sequencing to analyze these samples, and the results were evaluated by using alpha diversity, beta diversity and microbial composition analyses. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was also used to predict the metabolic pathways according to the Kyoto Encyclopedia of Genes and Genomes database. Results The alpha and beta diversity of the microbiota changed significantly in H. pylori infected individuals, but returned to baseline 42 days after eradication therapy. At the genus level, the abundances of Bacteroidetes , [Ruminococcus]_gnavus_group , Ruminococcaceae_Incertae_Sedis , Tuzzrealla , Butyricicoccus were significantly lower in the H. pylori infected group. Bacterial abundance was also dynamically changing during eradication treatment. In addition, PICRUST analysis found the levels of uronic acid metabolism, uncharacterized transport system, and biosynthesis of unsaturated fatty acids were higher in H. pylori infected individuals than in the non-infected group. Conclusions Intestinal microbiota diversity, composition, functional predictions altered significantly after H. pylori infection, and gradually returned to healthy control levels after the application of eradication therapy containing minocycline and metronidazole in one month and a half.

Background Talaromyces marneffei is an opportunistic pathogen that infects immunodeficient and immunocompromised patients. We presented a pediatric patient with a diagnosis of T. marneffei infection who was followed up in the Guangzhou Women and Children’s Medical Centre. Case presentation The child was a 5-year-old girl with persistent cough and gasping over 2 months who was confirmed with T. marneffei infection by bronchoalveolar lavage fluid culture and high-throughput sequencing technology. Human immunodeficiency virus (HIV) was negative according to a serum-specific antibody test. She was treated with amphotericin B and itraconazole as antifungal agents, with good clinical response. At follow-up, high-resolution computed tomography showed a mosaic sign in the whole lung field with a diagnosis of post-infectious bronchiolitis obliterans (PIBO) as the sequela. She has a mutated COPA gene with uncertain pathogenic potential on whole-exome sequencing. Conclusions Clinicians should consider PIBO as a possible sequela in an HIV-negative paediatric patient with T. marneffei infection.

Innate immunity is important for host defense by eliciting rapid anti-viral responses and bridging adaptive immunity. Here, we show that endogenous lipids released from virus-infected host cells activate lung γδ T cells to produce interleukin 17 A (IL-17A) for early protection against H1N1 influenza infection. During infection, the lung γδ T cell pool is constantly supplemented by thymic output, with recent emigrants infiltrating into the lung parenchyma and airway to acquire tissue-resident feature. Single-cell studies identify IL-17A-producing γδ T (Tγδ17) cells with a phenotype of TCRγδ hi CD3 hi AQP3 hi CXCR6 hi in both infected mice and patients with pneumonia. Mechanistically, host cell-released lipids during viral infection are presented by lung infiltrating CD1d + B-1a cells to activate IL-17A production in γδ T cells via γδTCR-mediated IRF4-dependent transcription. Reduced IL-17A production in γδ T cells is detected in mice either lacking B-1a cells or with ablated CD1d in B cells. Our findings identify a local host-immune crosstalk and define important cellular and molecular mediators for early innate defense against lung viral infection. Influenza A infection results in γδ T cell influx and production of IL-17 in the lungs. Here, the authors show that this effect is primed by CD1-restricted ligands that are released by infected cells and presented by B1a cells in the lungs.