Toll-like receptor 10 expression in B cells is negatively correlated with the progression of primary Sjögren's disease.

Primary Sjögren's Disease (pSjD) is considered a B cell-mediated disease. Toll-like receptor 10 (TLR10) is highly expressed in human B cells, indicating that TLR10 probably plays a vital role in pSjD. We examined TLR10 expression in peripheral B subsets of pSjD patients and analyzed their association with disease activity. We observed that TLR10 expression in total, naïve, memory, and switched memory B cells was significantly increased in low-activity pSjD patients as compared with healthy controls and high-activity patients. TLR10 expression in the above mentioned B subsets (except naïve B) was negatively correlated with serum levels of anti-SSA antibody and BAFF, respectively. Moreover, a higher proportion of high-activity pSjD patients was observed in TLR10 low- than high-expressed patients. Our study concluded that TLR10 expression in CD19+ B and memory B was negatively correlated with pSjD disease activity, suggesting that TLR10 might take part in the progression of pSjD.

Legionella septentrionalis sp. nov., isolated from aquatic environments in the northern PR China.

Four strains (km711T, km714, km542 and km524), representing a novel Legionella species, were isolated from aquatic environments in northern PR China. Cells were Gram-stain-negative, rod-shaped, microaerobic, motile and growth depended on l-cysteine. They grew at 25‒42 °C (optimum, 35‒37 °C) and could tolerate up to 1.5 % (w/v) NaCl (optimum, 0.5 %). The major fatty acids (>5 %) of the type strain km711T were C17 : 0 anteiso, C15 : 0 anteiso, iso-C16 : 0 and C16 : 1 ω7c and/or iso-C15 : 0 2OH. The pairwise comparison values were <96.1 % for 16S rRNA gene sequences, 23.3‒28.7 % interspecies variation for mip gene sequences, <93.6 % average nucleotide identity and <72.8 % average amino acid identity between these four strains and related type strains within the genus Legionella. The phylogenetic tree based on the four concatenated genes (16S rRNA, mip, rpoB and rnpB) and protein-concatamer tree based on concatenation of 21 protein markers both revealed that these four strains formed a separate phylogenetic branch cluster within the genus Legionella. The results of phenotypic and genotypic features suggest that these four strains represent a novel species of the genus Legionella, for which the name Legionella septentrionalis sp. nov. is proposed (type strain km711T=KCTC 15655T=NBRC 113219T).

Legionella qingyii sp. nov., isolated from water samples in China.

Three Legionella-like strains, designed km488T, km489 and km521, were isolated from freshwater samples in China. Cells were Gram-stain-negative, rod-shaped and non-spore-forming. Growth was observed on BCYEα agar, but not on BCYEα agar without l-cysteine, chocolate agar with PolyViteX or Columbia blood agar. The major fatty acids (>5 %) of strains km488T, km489 and km521 were C16 : 0, anteiso-C15 : 0, iso-C16 : 0 and anteiso-C17 : 0. The mip gene sequences (574 nt) showed the isolates were almost identical with more than 99.7 % sequence similarities, and closely matched to L. gormanii ATCC 33297T with 95.4-95.6 % sequence similarities. Phylogenetic analyses based on concatenated gene (16S rRNA, mip, rpoB and rnpB) sequences indicated that the isolates formed a distinct cluster along with L. gormanii within the genus Legionella. Matrix-assisted laser desorption ionization time-of-flight analyses also demonstrated a clear separation between the isolates and other closely and distantly related Legionella species. DNA-DNA hybridization studies demonstrated that the isolates were closely related (92.0 -95.0 % DNA-DNA relatedness) but differentiated from their phylogenetic neighbours (<70 % DNA-DNA relatedness). The whole genome of km488T was sequenced, and showed a G+C content of 37.8 mol%. Based on the findings from this polyphasic taxonomic study, the isolates are considered to represent a single novel species, for which the name Legionella qingyii sp. nov. is proposed. The type strain is km488T (KCTC 15636T=CCTCC AB 2018025T=NRBC 113223T).

Targeting single-nucleotide polymorphisms in the 16S rRNA gene to detect and differentiate Legionella pneumophila and non-Legionella pneumophila species.

A PCR-based method targeting single-nucleotide polymorphisms (SNPs) in the 16S rRNA gene was developed for differential identification of Legionella pneumophila and non-Legionella pneumophila. Based on the bioinformatics analysis for 176 Legionella 16S rRNA gene fragments of 56 different Legionella species, a set of SNPs, A(628)C(629) was found to be highly specific to L. pneumophila strains. A multiplex assay was designed that was able to distinguish sites with limited sequence heterogeneity between L. pneumophila and non-L. pneumophila in the targeted 16S rRNA gene. The assay amplified a 261-bp amplicon for Legionella spp. and a set of 203- and 97-bp amplicons only specific to L. pneumophila species. Among 49 ATCC strains and 284 Legionella isolates from environmental water and clinical samples, 100 % of L. pneumophila and non-L. pneumophila strains were correctly identified and differentiated by this assay. The assay presents a more rapid, sensitive and alternative method to the currently available PCR-sequencing detection and differentiation method.

Different distribution patterns of ten virulence genes in Legionella reference strains and strains isolated from environmental water and patients.

Virulence genes are distinct regions of DNA which are present in the genome of pathogenic bacteria and absent in nonpathogenic strains of the same or related species. Virulence genes are frequently associated with bacterial pathogenicity in genus Legionella. In the present study, an assay was performed to detect ten virulence genes, including iraA, iraB, lvrA, lvrB, lvhD, cpxR, cpxA, dotA, icmC and icmD in different pathogenicity islands of 47 Legionella reference strains, 235 environmental strains isolated from water, and 4 clinical strains isolated from the lung tissue of pneumonia patients. The distribution frequencies of these genes in reference or/and environmental L. pneumophila strains were much higher than those in reference non-L. pneumophila or/and environmental non-L. pneumophila strains, respectively. L. pneumophila clinical strains also maintained higher frequencies of these genes compared to four other types of Legionella strains. Distribution frequencies of these genes in reference L. pneumophila strains were similar to those in environmental L. pneumophila strains. In contrast, environmental non-L. pneumophila maintained higher frequencies of these genes compared to those found in reference non-L. pneumophila strains. This study illustrates the association of virulence genes with Legionella pathogenicity and reveals the possible virulence evolution of non-L. pneumophia strains isolated from environmental water.

Plasmodium infection reduces the volume of the viral reservoir in SIV-infected rhesus macaques receiving antiretroviral therapy.

BACKGROUND: Previous studies indicated that Plasmodium infection activates the immune system, including memory CD4+ T cells, which constitute the reservoir of human immunodeficiency virus type-1 (HIV-1). Therefore, we postulated that co-infection with malaria might activate the reservoir of HIV-1. To test this hypothesis, we used a rhesus macaque model of co-infection with malaria and simian immunodeficiency virus (SIV), along with antiretroviral therapy (ART). RESULTS: Our results showed that Plasmodium infection reduced both the replication-competent virus pool in resting CD4+ T cells and the integrated virus DNA (iDNA) load in peripheral blood mononuclear cells in the monkeys. This reduction might be attributable to malaria-mediated activation and apoptotic induction of memory CD4+ T cells. Further studies indicated that histone acetylation and NF-kappaB (NF-κB) activation in resting CD4+ T cells may also play an important role in this reduction. CONCLUSIONS: The findings of this work expand our knowledge of the interaction between these two diseases. As more HIV-1-infected individuals in malaria-endemic areas receive ART, we should explore whether any of the patients co-infected with Plasmodium experience virologic benefits.

Characterization of SARS-CoV-2-specific humoral immunity and associated factors in the healthy population post-vaccination.

OBJECTIVES: To investigate factors that may influence humoral immunity post-vaccination with a COVID-19-inactivated vaccine (SC2IV). METHODS: A total of 1596 healthy individuals from the Seventh Affiliated Hospital, Sun Yat-sen University (1217) and Shenzhen Baotian Hospital (379) were enrolled in this study among which 694 and 218 participants were vaccinated with two-dose SC2IV, respectively. Physical examination indices were recorded. The levels of neutralizing antibody (NA), Spike IgG, receptor-binding domain (RBD) IgG, RBD IgG + IgM + IgA, and nucleocapsid IgG of SARS-CoV-2 were measured by a non-virus ELISA kit. Multiple statistical analyses were carried out to identify factors that influence humoral immunity post-vaccination. RESULTS: The two-dosage vaccination could induce NA in more than 90 % of recipients. The NA has the strongest correlation with anti-RBD IgG. Age is the most important independent index that affects the NA level, while basophil count, creatine kinase-MB, mean corpuscular hemoglobin, the ratio of albumin to urine creatinine, and thyroglobulin antibody have relatively minor contributions. Indices that affect the NA level were different between males and females. Antibodies targeting other epitopes of SARS-CoV-2 were detected in recipients without anti-RBD. CONCLUSIONS: The factors identified in association with the NA level post-vaccination may help to evaluate the protective effect, risk of re-infection, the severity of symptoms, and prognosis for vaccine recipients in clinical.

Mpox virus mRNA-lipid nanoparticle vaccine candidates evoke antibody responses and drive protection against the Vaccinia virus challenge in mice.

In response to the human Mpox (hMPX) epidemic that began in 2022, there is an urgent need for a monkeypox vaccine. Here, we have developed a series of mRNA-lipid nanoparticle (mRNA-LNP)-based vaccine candidates that encode a collection of four highly conserved Mpox virus (MPXV) surface proteins involved in virus attachment, entry, and transmission, namely A29L, A35R, B6R, and M1R, which are homologs to Vaccinia virus (VACV) A27, A33, B5, and L1, respectively. Despite possible differences in immunogenicity among the four antigenic mRNA-LNPs, administering these antigenic mRNA-LNPs individually (5 µg each) or an average mixture of these mRNA-LNPs at a low dose (0.5 µg each) twice elicited MPXV-specific IgG antibodies and potent VACV-specific neutralizing antibodies. Furthermore, two doses of 5 µg of A27, B5, and L1 mRNA-LNPs or a 2 µg average mixture of the four antigenic mRNA-LNPs protected mice against weight loss and death after the VACV challenge. Overall, our data suggest that these antigenic mRNA-LNP vaccine candidates are both safe and efficacious against MPXV, as well as diseases caused by other orthopoxviruses.

Gastric cancer clinical characteristics and their altered trends in South China: An epidemiological study with 2,800 cases spanning 26 years.

Background: Gastric cancer (GC) is a serious threat to human health. The clinical GC characteristics in China may be impacted by changes in people's lifestyles and the promotion of early GC (EGC) screening. The present study aims to evaluate the recent trends of GC characteristics in South China and search for hazardous factors limiting the survival time of GC patients. Methods: Data on GC patients that were hospitalized in the Department of Digestive Center, the First Affiliated Hospital, Sun Yat-sen University, from 1994 to 2019 were collected and divided into two categories according to the time when the EGC screening began in China: the PRE group (previous 13 years, 1994-2006) and the PAS group (past 13 years, 2007-2019). Results: We found that, although the 5-year survival rate increased in the PAS group compared with the PRE group (P < 0.0001), patients with age ≥60 years or Borrmann type IV still had a worse prognosis. In the PAS group, the larger percentages of elderly patients and patients with Borrmann type IV in the lymphatic metastases (N1) group (41.0% vs. 51.1%, P = 0.0014) and stage IV subgroup (20.7% vs. 32.2%, P = 0.016), respectively, when compared with the PRE group, may have contributed to the poor outcome of GC. By comparing the odds ratio (OR) of 5-year overall survival (OS) in the two 13-year periods, female sex and T2 turned into risk factors because of a greater proportion of Borrmann type IV or elderly patients in the PAS group (OR = 0.983, 95% CI = 0.723-1.336 vs. OR = 1.277, 95% CI = 1.028-1.586 and OR = 1.545, 95% CI = 0.499-4.775 vs. OR = 2.227, 95% CI = 1.124-4.271, respectively). Conclusions: Despite the GC epidemiology changes, the overall prognosis of GC patients has improved in South China. However, old age and Borrmann type IV are still the major restrictions affecting the survival of GC patients, a situation which calls for additional attention.

Platelet dropping, bleeding and new treatment requirements in ITP patients after inactivated COVID-19 vaccination.

Significant decreases in platelet counts and ITP relapses have been documented in ITP patients receiving COVID-19 mRNA vaccines; however, the effect of the inactivated COVID-19 vaccine on ITP patients remains unclear. The present study aimed to investigate the impact of inactivated COVID-19 vaccines on ITP patients, with a focus on platelet dropping events, bleeding events/scores, and the requirement of a new round of treatment. A total of 118 ITP patients, with 97 chronic ITP and 21 persistent ITP, who received inactivated COVID-19 immunization were investigated retrospectively. Following vaccination (within 1 month), ITP patients reported platelet dropping (31.36 %), new bleeding events (22.88 %), increases in bleeding scores (23.73 %), and new treatment requirements (22.03 %). Among them, persistent ITP patients with disease duration of 3-12 months had higher ratios of the above adverse events (71.43 %, 57.14 %, 61.90 % and 71.43 %, respectively) than chronic ITP patients with duration > 1 year (22.68 %, 15.46 %, 15.46 % and 11.34 %, respectively); patients' disease duration was negatively correlated with platelet dropping events and new treatment requirements. Furthermore, logistic regression analysis also supported the above findings, revealing that persistent ITP patients had 9.40-9.70, 7.24-10.08, and 27.17-28.51 times incidence of having platelet dropping events, new bleeding events, and new treatment requirements after vaccination, respectively, when compared to chronic ITP patients. In conclusion, the present study demonstrates that after receiving inactivated COVID-19 vaccines, ITP patients may experience platelet dropping, which may lead to new bleeding events and the requirement of a new round of treatment for ITP recurrence. As a result, platelet level monitoring is crucial for ITP patients during the vaccination, especially those with persistent ITP.

Concept about the Virulence Factor of Legionella.

Pathogenic species of Legionella can infect human alveolar macrophages through Legionella-containing aerosols to cause a disease called Legionellosis, which has two forms: a flu-like Pontiac fever and severe pneumonia named Legionnaires' disease (LD). Legionella is an opportunistic pathogen that frequently presents in aquatic environments as a biofilm or protozoa parasite. Long-term interaction and extensive co-evolution with various genera of amoebae render Legionellae pathogenic to infect humans and also generate virulence differentiation and heterogeneity. Conventionally, the proteins involved in initiating replication processes and human macrophage infections have been regarded as virulence factors and linked to pathogenicity. However, because some of the virulence factors are associated with the infection of protozoa and macrophages, it would be more accurate to classify them as survival factors rather than virulence factors. Given that the molecular basis of virulence variations among non-pathogenic, pathogenic, and highly pathogenic Legionella has not yet been elaborated from the perspective of virulence factors, a comprehensive explanation of how Legionella infects its natural hosts, protozoans, and accidental hosts, humans is essential to show a novel concept regarding the virulence factor of Legionella. In this review, we overviewed the pathogenic development of Legionella from protozoa, the function of conventional virulence factors in the infections of protozoa and macrophages, the host's innate immune system, and factors involved in regulating the host immune response, before discussing a probably new definition for the virulence factors of Legionella.

Evolutionary dissection of monkeypox virus: Positive Darwinian selection drives the adaptation of virus-host interaction proteins.

The emerging and ongoing outbreak of human monkeypox (hMPX) in 2022 is a serious global threat. An understanding of the evolution of the monkeypox virus (MPXV) at the single-gene level may provide clues for exploring the unique aspects of the current outbreak: rapidly expanding and sustained human-to-human transmission. For the current investigation, alleles of 156 MPXV coding genes (which account for >95% of the genomic sequence) have been gathered from roughly 1,500 isolates, including those responsible for the previous outbreaks. Using a range of molecular evolution approaches, we demonstrated that intra-species homologous recombination has a negligible effect on MPXV evolution. Despite the fact that the majority of the MPXV genes (64.10%) were subjected to negative selection at the whole gene level, 10 MPXV coding genes (MPXVgp004, 010, 012, 014, 044, 098, 138, 178, 188, and 191) were found to have a total of 15 codons or amino acid sites that are known to evolve under positive Darwinian selection. Except for MPXVgp138, almost all of these genes encode proteins that interact with the host. Of these, five ankyrin proteins (MPXVgp004, 010, 012, 178, and 188) and one Bcl-2-like protein (MPXVgp014) are involved in poxviruses' host range determination. We discovered that the majority (80%) of positive amino acid substitutions emerged several decades ago, indicating that these sites have been under constant selection pressure and that more adaptable alleles have been circulating in the natural reservoir. This finding was also supported by the minimum spanning networks of the gene alleles. The three positive amino acid substitutions (T/A426V in MPXVgp010, A423D in MPXVgp012, and S105L in MPXVgp191) appeared in 2019 or 2022, indicating that they would be crucial for the virus' eventual adaptation to humans. Protein modeling suggests that positive amino acid substitutions may affect protein functions in a variety of ways. Further study should focus on revealing the biological effects of positive amino acid substitutions in the genes for viral adaptation to humans, virulence, transmission, and so on. Our study advances knowledge of MPXV's adaptive mechanism and provides insights for exploring factors that are responsible for the unique aspects of the current outbreak.

Correlation between thrombopoietin and inflammatory factors, platelet indices, and thrombosis in patients with sepsis: A retrospective study.

BACKGROUND: Thrombopoietin (TPO) is a primary regulator of thrombopoiesis in physiological conditions. TPO, in combination with its specific cytokine receptor c-Mpl, drives platelet production by inducing the proliferation and differentiation of megakaryocytes. However, the role of TPO in sepsis is not well determined. The elevated levels of TPO are often accompanied by a decrease of platelet count (PLT) in systemic infected conditions, which is contrary to the view that TPO promotes platelet production under physiological conditions. In addition, whether TPO mediates organ damage in sepsis remains controversial. AIM: To explore the relationships between TPO and inflammatory factors, platelet indices, and thrombotic indicators in sepsis. METHODS: A total of 90 patients with sepsis diagnosed and treated at the emergency medicine department of The First People's Hospital of Foshan between January 2020 and March 2021 were enrolled in this study. In addition, 110 patients without sepsis who came to the emergency medicine department were included as controls. Clinical and laboratory parameters including age, gender, TPO, blood cell count in peripheral blood, platelet indices, inflammatory factors such as high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-21, and IL-6, organ damage indicators, and thrombotic indicators were collected and analyzed by using various statistical approaches. RESULTS: The results showed that the TPO levels were higher in the sepsis group than in controls [86.45 (30.55, 193.1) vs 12.45 (0.64, 46.09) pg/mL, P < 0.001], but PLT was lower (P < 0.001). Multivariable analysis showed that white blood cell count (WBC) [odds ratio (OR) = 1.32; 95% confidence interval (CI): 1.01-1.722; P = 0.044], TPO (OR = 1.02; 95%CI: 1.01-1.04; P = 0.009), IL-21 (OR = 1.02; 95%CI: 1.00-1.03; P = 0.019), troponin I (OR = 55.20; 95%CI: 5.69-535.90; P = 0.001), and prothrombin time (PT) (OR = 2.24; 95%CI: 1.10-4.55; P = 0.027) were independent risk factors associated with sepsis. TPO levels were positively correlated with IL-21, IL-6, hs-CRP, creatinine, D-dimer, PT, activated prothrombin time, international normalized ratio, fibrinogen, WBC count, and neutrophil count, and negatively correlated with PLT, thrombin time, red blood cell count, and hemoglobin concentration (P < 0.05). Receiver operating characteristic analysis showed that TPO had fair predictive value in distinguishing septic patients and non-septic patients (the area under the curve: 0.788; 95%CI: 0.723-0.852; P < 0.001). With an optimized cutoff value (28.51 pg/mL), TPO had the highest sensitivity (79%) and specificity (65%). CONCLUSION: TPO levels are independently associated with sepsis. High TPO levels and low PLT suggest that TPO might be an acute-phase response protein in patients with infection.

Polysaccharide-Based Hydrogels for Wound Dressing: Design Considerations and Clinical Applications.

Wound management remains a worldwide challenge. It is undeniable that patients with problems such as difficulties in wound healing, metabolic disorder of the wound microenvironment and even severely infected wounds etc. always suffer great pain that affected their quality of lives. The selection of appropriate wound dressings is vital for the healing process. With the advances of technology, hydrogels dressings have been showing great potentials for the treatment of both acute wounds (e.g., burn injuries, hemorrhage, rupturing of internal organs/aorta) and chronic wounds such as diabetic foot and pressure ulcer. Particularly, in the past decade, polysaccharide-based hydrogels which are made up with abundant and reproducible natural materials that are biocompatible and biodegradable present unique features and huge flexibilities for modifications as wound dressings and are widely applicable in clinical practices. They share not only common characteristics of hydrogels such as excellent tissue adhesion, swelling, water absorption, etc., but also other properties (e.g., anti-inflammatory, bactericidal and immune regulation), to accelerate wound re-epithelialization, mimic skin structure and induce skin regeneration. Herein, in this review, we highlighted the importance of tailoring the physicochemical performance and biological functions of polysaccharide-based hydrogel wound dressings. We also summarized and discussed their clinical states of, aiming to provide valuable hints and references for the future development of more intelligent and multifunctional wound dressings of polysaccharide hydrogels.

Corrigendum: Antimicrobial susceptibility profiles and tentative epidemiological cutoff values of Legionella pneumophila from environmental water and soil sources in China.

[This corrects the article DOI: 10.3389/fmicb.2022.924709.].

Antimicrobial susceptibility profiles and tentative epidemiological cutoff values of Legionella pneumophila from environmental water and soil sources in China.

Legionnaires' disease (LD), caused by Legionella, including the most prevalent Legionella pneumophila, has been treated primarily with antibiotics. Environmental water and soil are the reservoirs for L. pneumophila. Studying antimicrobial susceptibility using a large number of isolates from various environmental sources and regions could provide an unbiased result. In the present study, antimicrobial susceptibility of 1464 environmental L. pneumophila isolates that were derived from various environmental water and soil sources of 12 cities in China to rifampin (RIF), erythromycin (ERY), clarithromycin (CLA), azithromycin (AZI), ciprofloxacin (CIP), moxifloxacin (MOX), levofloxacin (LEV), and doxycycline (DOX) was investigated, and minimum inhibitory concentration (MIC) data were obtained. We show that regarding macrolides, ERY was least active (MIC90 = 0.5 mg/L), while CLA was most active (MIC90 = 0.063 mg/L). A total of three fluoroquinolones have similar MICs on L. pneumophila. Among these antimicrobials, RIF was the most active agent, while DOX was the most inactive one. We observed different susceptibility profiles between serogroup 1 (sg1) and sg2-15 or between water and soil isolates from different regions. The ECOFFs were ERY and AZI (0.5 mg/L), RIF (0.002 mg/L), CIP, CLA and MOX (0.125 mg/L), LEV (0.063 mg/), and DOX (32 mg/L). Overall, two fluoroquinolone-resistant environmental isolates (0.14%) were first documented based on the wild-type MIC distribution. Not all azithromycin-resistant isolates (44/46, 95.65%) harbored the lpeAB efflux pump. The MICs of the ERY and CLA on the lpeAB + isolates were not elevated. These results suggested that the lpeAB efflux pump might be only responsible for AZI resistance, and undiscovered AZI-specific resistant mechanisms exist in L. pneumophila. Based on the big MIC data obtained in the present study, the same defense strategies, particularly against both CLA and RIF, may exist in L. pneumophila. The results determined in our study will guide further research on antimicrobial resistance mechanisms of L. pneumophila and could be used as a reference for setting clinical breakpoints and discovering antimicrobial-resistant isolates in the clinic, contributing to the antibiotic choice in the treatment of LD.

Presence of Viable, Clinically Relevant Legionella Bacteria in Environmental Water and Soil Sources of China.

The distribution of pathogenic Legionella in the environmental soil and water of China has not been documented yet. In this study, Legionella was detected in 129 of 575 water (22.43%) and 41 of 442 soil samples (9.28%) by culture. Twelve Legionella species were identified, of which 11 were disease-associated. Of the Legionella-positive samples, 109 of 129 (84.50%) water and 29 of 41 (70.73%) soil were positive for L. pneumophila, which accounted for about 75% of Legionella isolates in both water and soil, suggesting L. pneumophila was the most frequent species. Soil showed a higher diversity of Legionella spp. as compared with water (0.6279 versus 0.4493). In contrast, serogroup (sg) 1 was more prevalent among L. pneumophila isolates from water than from soil (26.66% versus 12.21%). Moreover, many disease-associated sequence types (STs) of L. pneumophila were found in China. Intragenic recombination was acting on L. pneumophila from both water and soil. Phylogeny, population structure, and molecular evolution analyses revealed a probable existence of L. pneumophila isolates with a special genetic background that is more adaptable to soil or water sources and a small proportion of genetic difference between water and soil isolates. The detection of viable, clinically relevant Legionella demonstrates soil as another source for harboring and dissemination of pathogenic Legionella bacteria in China. Future research should assess the implication in public health with the presence of Legionella in the soil and illustrate the genetic and pathogenicity difference of Legionella between water and soil, particularly the most prevalent L. pneumophila. IMPORTANCE Pathogenic Legionella spp. is the causative agent of Legionnaires' disease (LD), and L. pneumophila is the most common one. Most studies have focused on L. pneumophila from water and clinical samples. However, the soil is another important reservoir for this bacterium, and the distribution of Legionella spp. in water and soil sources has not been compared and documented in China yet. Discovering the distribution of Legionella spp. and L. pneumophila in the two environments may help a deep understanding of the pathogenesis and molecular evolution of the bacterium. Our research systematically uncovered the distributions of Legionella spp. in different regions and sources (e.g., water and soil) of China. Moreover, phylogeny, population structure, and molecular evolution study revealed the possible existence of L. pneumophila with a special genetic background that is more adaptable to soil or water sources, and genetic difference may exist.

Identification of Peptoniphilus vaginalis-Like Bacteria, Peptoniphilus septimus sp. nov., From Blood Cultures in a Cervical Cancer Patient Receiving Chemotherapy: Case and Implications.

A 39-year-old woman with a 3-year human papillomavirus (HPV) 18 infection history was admitted to the hospital for a 16-day history of vaginal bleeding after sex. She was diagnosed with cervical cancer based on the results of the electronic colposcopy, cervical cytology, microscopy, and magnetic resonance imaging (MRI). Then, she received chemotherapy, with paclitaxel 200 mg (day 1), cisplatin 75 mg (day 2), and bevacizumab 700 mg (day 3) twice with an interval of 27 days. During the examination for the diagnosis and treatment, many invasive operations, including removal of intrauterine device, colposcopy, and ureteral dilatation, were done. After that, the patient was discharged and entered the emergency department about 2.5 months later with a loss of consciousness probably caused by septic shock. The patient finally died of multiple organ failure and bacterial infection, although she has received antimicrobial therapy. The blood cultures showed a monobacterial infection with an anaerobic Gram-positive bacterial strain, designated as SAHP1. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) indicated that the patient was infected with Peptoniphilus asaccharolyticus, while molecular analysis and genome-based taxonomy confirmed the infection with a novel Peptoniphilus species that has a close genetic relationship with Peptoniphilus vaginalis and proposed provisionally as Peptoniphilus septimus sp. nov., which may also act as a commensal of the human vagina. Genomic features of SAHP1 have been fully described, and comparative genomic analysis reveals the known prokaryote relative of Peptoniphilus septimus sp. nov. in the genus Peptoniphilus. The invasive operations on the genital tract during the diagnosis and treatment of the patient and the tumor tissue damage and bleeding may have a certain role in the bloodstream infection. This study casts a new light on the Peptoniphilus bacteria and prompts clinicians to include anaerobic blood cultures as part of their blood culture procedures, especially on patients with genital tract tumors. Furthermore, due to the incomplete database and unsatisfying resolution of the MALDI-TOF MS for Peptoniphilus species identification, molecular identification, especially whole-genome sequencing, is required for those initially identified as bacteria belonging to Peptoniphilus in the clinical laboratory.

Tanshinone IIA Has a Potential Therapeutic Effect on Kawasaki Disease and Suppresses Megakaryocytes in Rabbits With Immune Vasculitis.

Background and Objective: It is urgent to find out an alternative therapy for Kawasaki disease (KD) since around 20% patients are resistant to intravenous immunoglobulin (IVIG) or aspirin. Tanshinone IIA is the active component of the traditional Chinese medicine Danshen (Salvia miltiorrhiza), which has anti-inflammatory and anti-platelet properties; however, whether or not tanshinone IIA has a therapeutic effect on KD remains unclear. Therefore, the present study aimed to examine the effect of tanshinone IIA on KD patients and rabbits with immune vasculitis, and to identify the potential mechanisms with special emphasis on megakaryopoiesis and megakaryocytic apoptosis. Methods: Kawasaki disease patients were recruited and prescribed with tanshinone IIA in the absence or presence of aspirin and IVIG, and the inflammatory responses and platelet functions were determined. Megakaryocytes (MKs) isolated from rabbits with immune vasculitis and human megakaryocytic CHRF-288-11 cells were treated with tanshinone IIA to examine the colony forming unit (CFU) and apoptosis, respectively. Microarray assay was conducted to identify potential targets of tanshinone IIA-induced apoptosis. Results: Tanshinone IIA reduced the serum levels of C-reactive protein (CRP), interleukin (IL)-1ß, IL-6, and P-selectin in KD patients; such inhibitory effect was more significant compared to aspirin and IVIG. It also dose-dependently lowered the levels of tumor necrosis factor (TNF)-α and IL-8 in peripheral blood mononuclear cells isolated from KD patients. In rabbits with immune vasculitis, tanshinone IIA significantly reduced the serum levels of proinflammatory cytokines and platelet functions. In addition, tanshinone IIA significantly decreased the number of bone marrow MKs and inhibited the Colony Forming Unit-Megakaryocyte (CFU-MK) formation. In human megakaryocytic CHRF-288-11 cells, tanshinone IIA induced caspase-dependent apoptosis, probably through up-regulating TNF receptor superfamily member 9 (TNFRSF9) and the receptor (TNFRSF)-interacting serine/threonine-protein kinase 1 (RIPK1), which may contribute to its anti-platelet and anti-inflammatory properties. Conclusion: Tanshinone IIA exerts better anti-inflammatory and anti-platelet effects in treating KD patients than aspirin and IVIG. It attenuates immune vasculitis likely by inhibiting IL-mediated megakaryopoiesis and inducing TNFRSF9/RIPK1/caspase-dependent megakaryocytic apoptosis. The findings therefore suggest that tanshinone IIA may be a promising alternative therapy for the treatment of KD.