The multifaceted role of macrophage mitophagy in SiO2-induced pulmonary fibrosis: A brief review.

Prolonged exposure to environments with high concentrations of crystalline silica (CS) can lead to silicosis. Macrophages play a crucial role in the pathogenesis of silicosis. In the process of silicosis, silica (SiO2) invades alveolar macrophages (AMs) and induces mitophagy which usually exists in three states: normal, excessive, and/or deficiency. Different mitophagy states lead to corresponding toxic responses, including successful macrophage repair, injury, necrosis, apoptosis, and even pulmonary fibrosis. This is a complex process accompanied by various cytokines. Unfortunately, the details have not been fully systematically summarized. Therefore, it is necessary to elucidate the role of macrophage mitophagy in SiO2-induced pulmonary fibrosis by systematic analysis on the literature reports. In this review, we first summarized the current data on the macrophage mitophagy in the development of SiO2-induced pulmonary fibrosis. Then, we introduce the molecular mechanism on how SiO2-induced mitophagy causes pulmonary fibrosis. Finally, we focus on introducing new therapies based on newly developed mitophagy-inducing strategies. We conclude that macrophage mitophagy plays a multifaceted role in the progression of SiO2-induced pulmonary fibrosis, and reprogramming the macrophage mitophagy state accordingly may be a potential means of preventing and treating pulmonary fibrosis.

The role of mitochondrial dysfunction in macrophages on SiO2 -induced pulmonary fibrosis: A review.

Several epidemiologic and toxicological studies have widely regarded that mitochondrial dysfunction is a popular molecular event in the process of silicosis from different perspectives, but the details have not been systematically summarized yet. Thus, it is necessary to investigate how silica dust leads to pulmonary fibrosis by damaging the mitochondria of macrophages. In this review, we first introduce the molecular mechanisms that silica dust induce mitochondrial morphological and functional abnormalities and then introduce the main molecular mechanisms that silica-damaged mitochondria induce pulmonary fibrosis. Finally, we conclude that the mitochondrial abnormalities of alveolar macrophages caused by silica dust are involved deeply in the pathogenesis of silicosis through these two sequential mechanisms. Therefore, reducing the silica-damaged mitochondria will prevent the potential occurrence and fatality of the disease in the future.

Core gut microbes Cloacibacterium and Aeromonas associated with different gastropod species could be persistently transmitted across multiple generations.

BACKGROUND: Studies on the gut microbiota of animals have largely focused on vertebrates. The transmission modes of commensal intestinal bacteria in mammals have been well studied. However, in gastropods, the relationship between gut microbiota and hosts is still poorly understood. To gain a better understanding of the composition of gut microbes and their transmission routes in gastropods, a large-scale and long-term experiment on the dynamics and transmission modes of gut microbiota was conducted on freshwater snails. RESULTS: We analyzed 244 microbial samples from the digestive tracts of freshwater gastropods and identified Proteobacteria and Bacteroidetes as dominant gut microbes. Aeromonas, Cloacibacterium, and Cetobacterium were identified as core microbes in the guts, accounting for over 50% of the total sequences. Furthermore, both core bacteria Aeromonas and Cloacibacterium, were shared among 7 gastropod species and played an important role in determining the gut microbial community types of both wild and cultured gastropods. Analysis of the gut microbiota at the population level, including wild gastropods and their offspring, indicated that a proportion of gut microbes could be consistently vertically transmitted inheritance, while the majority of the gut microbes resulted from horizontal transmission. Comparing cultured snails to their wild counterparts, we observed an increasing trend in the proportion of shared microbes and a decreasing trend in the number of unique microbes among wild gastropods and their offspring reared in a cultured environment. Core gut microbes, Aeromonas and Cloacibacterium, remained persistent and dispersed from wild snails to their offspring across multiple generations. Interestingly, under cultured environments, the gut microbiota in wild gastropods could only be maintained for up to 2 generations before converging with that of cultured snails. The difference observed in gut bacterial metabolism functions was associated with this transition. Our study also demonstrated that the gut microbial compositions in gastropods are influenced by developmental stages and revealed the presence of Aeromonas and Cloacibacterium throughout the life cycle in gastropods. Based on the dynamics of core gut microbes, it may be possible to predict the health status of gastropods during their adaptation to new environments. Additionally, gut microbial metabolic functions were found to be associated with the adaptive evolution of gastropods from wild to cultured environments. CONCLUSIONS: Our findings provide novel insights into the dynamic processes of gut microbiota colonization in gastropod mollusks and unveil the modes of microbial transmission within their guts. Video Abstract.

Risk Factors of Exchange Blood Transfusion in Infants With Severe Pertussis.

Exchange blood transfusion (ET) reportedly improves the outcomes of the patients with severe pertussis accompanied with deadly complications continued to worsen despite intensive therapeutic measures. This study assessed the medical records of 12 patients with severe pertussis requiring ET therapy who were admitted to our medical center. Of the 12 patients requiring ET therapy, 8 survived and 4 died. The independent risk factors for requiring ET therapy in infants with severe pertussis were T ≥ 38.5°C (odds ratio [OR], 11.697; 95% confidence interval [CI], 1.325-262.184; P = .046), C-reactive protein (CRP) >30 mg/L (OR, 62.393; 95% CI, 6.264-2381.773; P = .004), and WBC > 40.0 × 109/L (OR, 68.509; 95% CI, 8.118-1829.695; P = .001). ET therapy worked effectively for our severe pertussis cases. When the severe pertussis patients with T ≥ 38.5°C, CRP >30 mg/L, and WBC > 40.0 × 109/L, ET therapy might be taken into consideration.

Metagenome-Assembled Genomes Reveal Mechanisms of Carbohydrate and Nitrogen Metabolism of Schistosomiasis-Transmitting Vector Biomphalaria Glabrata.

Biomphalaria glabrata transmits schistosomiasis mansoni which poses considerable risks to hundreds of thousands of people worldwide, and is widely used as a model organism for studies on the snail-schistosome relationship. Gut microbiota plays important roles in multiple aspects of host including development, metabolism, immunity, and even behavior; however, detailed information on the complete diversity and functional profiles of B. glabrata gut microbiota is still limited. This study is the first to reveal the gut microbiome of B. glabrata based on metagenome-assembled genome (MAG). A total of 28 gut samples spanning diet and age were sequenced and 84 individual microbial genomes with ≥ 70% completeness and ≤ 5% contamination were constructed. Bacteroidota and Proteobacteria were the dominant bacteria in the freshwater snail, unlike terrestrial organisms harboring many species of Firmicutes and Bacteroidota. The microbial consortia in B. glabrata helped in the digestion of complex polysaccharide such as starch, hemicellulose, and chitin for energy supply, and protected the snail from food poisoning and nitrate toxicity. Both microbial community and metabolism of B. glabrata were significantly altered by diet. The polysaccharide-degrading bacterium Chryseobacterium was enriched in the gut of snails fed with high-digestibility protein and high polysaccharide diet (HPHP). Notably, B. glabrata as a mobile repository can escalate biosafety issues regarding transmission of various pathogens such as Acinetobacter nosocomialis and Vibrio parahaemolyticus as well as multiple antibiotic resistance genes in the environment and to other organisms. IMPORTANCE The spread of aquatic gastropod Biomphalaria glabrata, an intermediate host of Schistosoma mansoni, exacerbates the burden of schistosomiasis disease worldwide. This study provides insights into the importance of microbiome for basic biological activities of freshwater snails, and offers a valuable microbial genome resource to fill the gap in the analysis of the snail-microbiota-parasite relationship. The results of this study clarified the reasons for the high adaptability of B. glabrata to diverse environments, and further illustrated the role of B. glabrata in accumulation of antibiotic resistance in the environment and spread of various pathogens. These findings have important implications for further exploration of the control of snail dissemination and schistosomiasis from a microbial perspective.

Bacillus subtilis Attenuates Hepatic and Intestinal Injuries and Modulates Gut Microbiota and Gene Expression Profiles in Mice Infected with Schistosoma japonicum.

Parasitic infection can induce pathological injuries and impact the gut microbiota diversity and composition of the host. Bacillus subtilis is a nonpathogenic and noninvasive probiotic bacterium for humans and other animals, playing an important role in improving the host immune system's ability to respond to intestinal and liver diseases and modulating gut microbiota. However, whether B. subtilis can impact biological functions in Schistosoma japonicum-infected mice is unclear. This study used oral administration (OA) of B. subtilis to treat mice infected with S. japonicum. We evaluated changes in the gut microbiota of infected mice using 16 S rRNA gene sequencing and differentially expressed gene profiles using transcriptome sequencing after OA B. subtilis. We found that OA B. subtilis significantly attenuated hepatic and intestinal pathological injuries in infected mice. The gut microbiota of mice were significantly altered after S. japonicum infection, while OA B. subtilis remodel the diversity and composition of gut microbiomes of infected mice. We found that the S. japonicum-infected mice with OA B. subtilis had an overabundance of the most prevalent bacterial genera, including Bacteroides, Enterococcus, Lactobacillus, Blautia, Lachnoclostridium, Ruminiclostridium, and Enterobacter. Transcriptomic analysis of intestinal tissues revealed that OA B. subtilis shaped the intestinal microenvironment of the host responding to S. japonicum infection. Differentially expressed genes were classified into KEGG pathways between S. japonicum-infected mice and those without included cell adhesion molecules, intestinal immune network for IgA production, hematopoietic cell lineage, Fc epsilon RI signaling pathway, Th1 and Th2 cell differentiation, Th17 cell differentiation, calcium signaling pathway, Fc gamma R-mediated phagocytosis, chemokine signaling pathway, phospholipase D signaling pathway, NF-kappa B signaling pathway, B cell receptor signaling pathway, pancreatic secretion, and phagosome. In conclusion, our findings showed that OA B. subtilis alleviates pathological injuries and regulates gene expression, implying that B. subtilis supplementation may be a potential therapeutic strategy for schistosomiasis. Our study may highlight the value of probiotics as a beneficial supplementary therapy during human schistosomiasis, but further studies are needed.

Mortality risk factors among hospitalized children with severe pertussis.

BACKGROUND: Some children hospitalized for severe pertussis need intensive care; moreover, some children die because of deterioration alone or in combination with other complications. The purpose of this study was to identify the mortality risk factors among hospitalized children with severe pertussis. METHODS: This study evaluated the medical records of 144 hospitalized children with severe pertussis at the Guangzhou Women and Children's Medical Centre between January 2016 and December 2019. RESULTS: The median age of patients was 2 months (IQR 1-4 months), with 90.3% of the patients aged < 6 months and 56.9% of the patients aged < 3 months. A total of 38 patients were admitted to intensive care unit (ICU), 13 patients died, and the mortality of severe pertussis was 34.2%, with patients younger than 6 weeks accounting for 76.9% of the deaths. On the multivariate analysis, the independent risk factors for death were WBC > 70.0 × 109/L (odds ratio [OR], 230.66; 95% confidence interval [CI], 5.16-10,319.09 P = 0.005) and pulmonary hypertension (PH) (OR 323.29; 95% CI 16.01-6529.42; P < 0.001). CONCLUSION: Severe pertussis mainly occurred in children aged < 3 months. The mortality of severe pertussis was 34.2%, with patients younger than 6 weeks accounting for the majority of the deaths. We recommend the first dose of diphtheria-tetanus-pertussis (DTP) should be advanced to the age of 2 months or even 6 weeks. The presence of a WBC > 70.0 × 109/L and PH were the prognostic independent variables associated with death.

Heightened Local Th17 Cell Inflammation Is Associated with Severe Community-Acquired Pneumonia in Children under the Age of 1 Year.

Severe community-acquired pneumonia (sCAP) early in life is a leading cause of morbidity, mortality, and irreversible sequelae. Herein, we report the clinical, etiological, and immunological characteristics of 62 children age < 1 year. We measured 27 cytokines in plasma and bronchoalveolar lavage (BAL) from 62 children age < 1 year who were diagnosed with CAP, and then, we analyzed correlations among disease severity, clinical parameters, and etiology. Of the entire cohort, three cytokines associated with interleukin-17- (IL-17-) producing helper T cells (Th17 cells), IL-1ß, IL-6, and IL-17, were significantly elevated in sCAP patients with high fold changes (FCs); in BAL, these cytokines were intercorrelated and associated with blood neutrophil counts, Hb levels, and mixed bacterial-viral infections. BAL IL-1ß (area under the curve (AUC) 0.820), BAL IL-17 (AUC 0.779), and plasma IL-6 (AUC 0.778) had remarkable predictive power for sCAP. Our findings revealed that increased local Th17 cell immunity played a critical role in the development of sCAP in children age < 1 year. Th17 cell-related cytokines could serve as local and systemic inflammatory indicators of sCAP in this age group.

The potential risk of Schistosoma mansoni transmission by the invasive freshwater snail Biomphalaria straminea in South China.

Schistosomes infect more than 200 million people worldwide, and globally, over 700 million people are at risk of infection. The snail Biomphalaria straminea, as one of the intermediate hosts of Schistosoma mansoni, consecutively invaded Hong Kong in 1973, raising great concern in China. In this study, a malacological survey was conducted over a period of four years, and investigations were performed on the mechanism of susceptibility of B. straminea to S. mansoni. B. straminea was investigated in China from 2014 to 2018. Out of 185 investigated sites, 61 were positive for stages of black B. straminea (BBS), which shows pigmented spots. Twenty of the 61 sites were positive for red B. straminea (RBS), which is partially albino and red colored. Phylogenetic analyses based on cox1 and 18S rRNA sequences demonstrated that both phenotypes were clustered with Brazilian strains. No S. mansoni infections were detected in field-collected snail. However, in laboratory experiments, 4.17% of RBS were susceptible to a Puerto Rican strain of S. mansoni, while BBS was not susceptible. The highest susceptibility rate (70.83%) was observed in the F2 generation of RBS in lab. The density of RBS has increased from south to north and from west to east in Guangdong since 2014. Five tyrosinase tyrosine metabolism genes were upregulated in BBS. Transcriptome comparisons of RBS and BBS showed that ficolin, C1q, MASP-like, and membrane attack complex (MAC)/perforin models of the complement system were significantly upregulated in BBS. Our study demonstrated that B. straminea is widely distributed in Hong Kong and Guangdong Province, which is expanding northwards very rapidly as a consequence of its adaptation to local environments. Our results suggest that B. straminea from South China is susceptible to S. mansoni, implying the high potential for S. mansoni transmission and increased S. mansoni infection risk in China.