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The continual emergence of tick-borne rickettsioses has garnered widespread global attention. Candidatus Rickettsia barbariae ( Candidatus R. barbariae), which emerged in Italy in 2008, has been detected in humans from northwestern China. However, the lack of Candidatus R. barbariae genome and isolated strains limits the understanding of its biological characteristics and genomic features. Here, we isolated the Rickettsia for the first time from eggs of Rhipicephalus turanicus in northwestern China, and assembled its whole genome after next-generation sequencing, so we modified the proposed name to Rickettsia barbariae ( R. barbariae ) to conform to the International Code of Nomenclature of Prokaryotes. Phylogenetic analysis based on the whole genome revealed that it was most closely related to the pathogenic Rickettsia parkeri and Rickettsia africae . All virulence factors, present in the pathogenic spotted fever group rickettsiae, were identified in the R. barbariae isolate. These findings highlight the pathogenic potential of R. barbariae and the necessity for enhanced surveillance of the emerging Rickettsia in the human population.

Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins, showing a potential threat to humans. Here we report the infectivity and pathogenicity of the SARS-CoV-2-related virus, PCoV-GX/P2V, which was isolated from a Malayan pangolin (Manis javanica). PCoV-GX/P2V could grow in human hepatoma, colorectal adenocarcinoma cells, and human primary nasal epithelial cells. It replicated more efficiently in cells expressing human angiotensin-converting enzyme 2 (hACE2) as SARS-CoV-2 did. After intranasal inoculation to the hACE2-transgenic mice, PCoV-GX/P2V not only replicated in nasal turbinate and lungs, but also caused interstitial pneumonia, characterized by infiltration of mixed inflammatory cells and multifocal alveolar hemorrhage. Existing population immunity established by SARS-CoV-2 infection and vaccination may not protect people from PCoV-GX/P2V infection. These findings further verify the hACE2 utility of PCoV-GX/P2V by in vivo experiments using authentic viruses and highlight the importance for intensive surveillance to prevent possible cross-species transmission., (© 2024. Science China Press.)

Spotted fever group rickettsiae (SFGR) are obligate intracellular bacteria that cause spotted fever. The limitations of gene manipulation pose great challenges to studying the infection mechanisms of Rickettsia. By combining bioorthogonal metabolism and click chemistry, we developed a method to label R. heilongjiangensis via azide moieties and achieved rapid pathogen localization without complex procedures. Moreover, we constructed a C57BL/6 mice infection model by simulating tick bites and discovered that the stomach is the target organ of R. heilongjiangensis infection through in vivo imaging systems, which explained the occurrence of gastrointestinal symptoms following R. heilongjiangensis infection in some cases. This study offers a unique perspective for subsequent investigations into the pathogenic mechanisms of SFGR and identifies a potential target organ for R. heilongjiangensis., (© 2024. The Author(s).)

The emerging evidence of human infections with emerging viruses suggests their potential public health importance. A novel taxon of viruses named Statoviruses (for stool-associated Tombus-like viruses) was recently identified in the gastrointestinal tracts of multiple mammals. Here we report the discovery of respiratory Statovirus-like viruses (provisionally named Restviruses) from the respiratory tracts of five patients experiencing acute respiratory disease with Human coronavirus OC43 infection through the retrospective analysis of meta-transcriptomic data. Restviruses shared 53.1%-98.8% identities of genomic sequences with each other and 39.9%-44.3% identities with Statoviruses. The phylogenetic analysis revealed that Restviruses together with a Stato-like virus from nasal-throat swabs of Vietnamese patients with acute respiratory disease, formed a well-supported clade distinct from the taxon of Statoviruses. However, the consistent genome characteristics of Restviruses and Statoviruses suggested that they might share similar evolutionary trajectories. These findings warrant further studies to elucidate the etiological and epidemiological significance of the emerging Restviruses., (© 2024 Wiley Periodicals LLC.)

We recently detected a HKU4-related coronavirus in subgenus Merbecovirus (named pangolin-CoV-HKU4-P251T) from a Malayan pangolin 1 . Here we report isolation and characterization of pangolin-CoV-HKU4-P251T, the genome sequence of which is closest to that of a coronavirus from the greater bamboo bat (Tylonycteris robustula) in Yunnan Province, China, with a 94.3% nucleotide identity. Pangolin-CoV-HKU4-P251T is able to infect human cell lines, and replicates more efficiently in cells that express human-dipeptidyl-peptidase-4 (hDPP4)-expressing and pangolin-DPP4-expressing cells than in bat-DPP4-expressing cells. After intranasal inoculation with pangolin-CoV-HKU4-P251, hDPP4-transgenic female mice are likely infected, showing persistent viral RNA copy numbers in the lungs. Progressive interstitial pneumonia developed in the infected mice, characterized by the accumulation of macrophages, and increase of antiviral cytokines, proinflammatory cytokines, and chemokines in lung tissues. These findings suggest that the pangolin-borne HKU4-related coronavirus has a potential for emerging as a human pathogen by using hDPP4., (© 2024. The Author(s).)

Background: Human babesiosis is a worldwide disease caused by intraerythrocytic protozoa of the genus Babesia. It is transmitted by bites from ixodid ticks, and mechanically transmitted by blood transfusion. It is primarily treated with quinine and/or atovaquone, which are not readily available in China. In this study, we developed a novel treatment regimen involving doxycycline monotherapy in a patient with severe Babesia venatorum infection as an alternative therapeutic medication. The aim of our study is to provide a guidance for clinical practice treatment of human babesiosis., Case Presentation: A 73-year-old man who had undergone splenectomy and blood transfusion 8 years prior, presented with an unexplained fever, headache, and thrombocytopenia, and was admitted to the Fifth Medical Center of the PLA General Hospital. He was diagnosed with B. venatorum infection by morphological review of thin peripheral blood smears, which was confirmed by multi-gene polymerase chain reaction (PCR), and sequencing of the entire 18s rRNA and partial β-tubulin encoding genes, as well as isolation by animal inoculation. The doxycycline monotherapy regimen (peros, 0.1 g bisindie) was administered following pharmacological guidance and an effective outcome was observed. The patient recovered rapidly following the doxycycline monotherapy. The protozoan load in peripheral blood samples decreased by 88% in hematocrit counts after 8 days, and negative PCR results were obtained after 90 days of follow-up at the hospital. The treatment lasted for 3 months without any side effects or sequelae. The nine-month follow-up survey of the patient did not reveal any signs of recrudescence or anti-babesial tolerance., Conclusions: We have reported a clinical case of successful doxycycline monotherapy for human babesiosis caused by B. venatorum, which provides an optional medical intervention for human babesiosis., (© 2023. The Author(s).)

Background: The impact of host skin microbiome on horizontal transmission of tick-borne pathogens , and of pathogen associated transstadial and transovarial changes in tick microbiome are largely unknown, but are important to control increasingly emerging tick-borne diseases worldwide., Methods: Focusing on a rickettsiosis pathogen, Rickettsia raoultii, we used R. raoultii-positive and R. raoultii-negative Dermacentor spp. tick colonies to study the involvement of skin microbiota in cutaneous infection with rickettsiae in laboratory mice, and the function of the tick microbiome on maintenance of rickettsiae through all tick developmental stages (eggs, larvae, nymphs, adults) over two generations., Results: We observed changes in the skin bacteria community, such as Chlamydia, not only associated with rickettsial colonization but also with tick feeding on skin. The diversity of skin microbiome differed between paired tick-bitten and un-bitten sites. For vertical transmission, significant differences in the tick microbiota between pathogenic rickettsia-positive and -negative tick chorts was observed across all developmental stages at least over two generations, which appeared to be a common pattern not only for R. raoultii but also for another pathogenic species, Candidatus Rickettsia tarasevichiae. More importantly, bacterial differences were complemented by functional shifts primed for genetic information processing during blood feeding. Specifically, the differences in tick microbiome gene repertoire between pathogenic Rickettsia-positive and -negative progenies were enriched in pathways associated with metabolism and hormone signals during vertical transmission., Conclusions: We demonstrate that host skin microbiome might be a new factor determining the transmission of rickettsial pathogens through ticks. While pathogenic rickettsiae infect vertebrate hosts during blood-feeding by the tick, they may also manipulate the maturation of the tick through changing the functional potential of its microbiota over the tick's life stages. The findings here might spur the development of new-generation control methods for ticks and tick-borne pathogens. Video Abstract., (© 2023. The Author(s).)

Mass production of high-quality synthetic SAR training imagery is essential for boosting the performance of deep-learning (DL)-based SAR automatic target recognition (ATR) algorithms in an open-world environment. To address this problem, we exploit both the widely used Moving and Stationary Target Acquisition and Recognition (MSTAR) SAR dataset and the Synthetic and Measured Paired Labeled Experiment (SAMPLE) dataset, which consists of selected samples from the MSTAR dataset and their computer-generated synthetic counterparts. A series of data augmentation experiments are carried out. First, the sparsity of the scattering centers of the targets is exploited for new target pose synthesis. Additionally, training data with various clutter backgrounds are synthesized via clutter transfer, so that the neural networks are better prepared to cope with background changes in the test samples. To effectively augment the synthetic SAR imagery in the SAMPLE dataset, a novel contrast-based data augmentation technique is proposed. To improve the robustness of neural networks against out-of-distribution (OOD) samples, the SAR images of ground military vehicles collected by the self-developed MiniSAR system are used as the training data for the adversarial outlier exposure procedure. Simulation results show that the proposed data augmentation methods are effective in improving both the target classification accuracy and the OOD detection performance. The purpose of this work is to establish the foundation for large-scale, open-field implementation of DL-based SAR-ATR systems, which is not only of great value in the sense of theoretical research, but is also potentially meaningful in the aspect of military application.

The increasing prevalence and expanding distribution of tick-borne viruses globally have raised health concerns, but the full repertoire of the tick virome has not been assessed. We sequenced the meta-transcriptomes of 31 different tick species in the Ixodidae and Argasidae families from across mainland China, and identified 724 RNA viruses with distinctive virome compositions among genera. A total of 1,801 assembled and complete or nearly complete viral genomes revealed an extensive diversity of genome architectures of tick-associated viruses, highlighting ticks as a reservoir of RNA viruses. We examined the phylogenies of different virus families to investigate virome evolution and found that the most diverse tick-associated viruses are positive-strand RNA virus families that demonstrate more ancient divergence than other arboviruses. Tick-specific viruses are often associated with only a few tick species, whereas virus clades that can infect vertebrates are found in a wider range of tick species. We hypothesize that tick viruses can exhibit both 'specialist' and 'generalist' evolutionary trends. We hope that our virome dataset will enable much-needed research on vertebrate-pathogenic tick-associated viruses., (© 2023. The Author(s).)

Rickettsiae are obligate intracellular bacteria that can cause life-threatening illnesses. There is an ongoing debate as to whether established infections by one Rickettsia species preclude the maintenance of the second species in ticks. Here, we identified two Rickettsia species in inoculum from Haemaphysalis montgomeryi ticks and subsequently obtained pure isolates of each species by plaque selection. The two isolates were classified as a transitional group and spotted fever group rickettsiae and named Rickettsia hoogstraalii str CS and Rickettsia rhipicephalii str EH, respectively. The coinfection of these two Rickettsia species was detected in 25.6% of individual field-collected H. montgomeryi. In cell culture infection models, R. hoogstraalii str CS overwhelmed R. rhipicephalii str EH with more obvious cytopathic effects, faster plaque formation, and increased cellular growth when cocultured, and R. hoogstraalii str CS seemed to polymerize actin tails differently from R. rhipicephalii str EH in vitro . This work provides a model to investigate the mechanisms of both Rickettsia - Rickettsia and Rickettsia -vector interactions. IMPORTANCE The rickettsiae are a group of obligate intracellular Gram-negative bacteria that include human pathogens causing an array of clinical symptoms and even death. There is an important question in the field, that is whether one infection can block the superinfection of other rickettsiae. This work demonstrated the coinfection of two Rickettsia species in individual ticks and further highlighted that testing the rickettsial competitive exclusion hypothesis will undoubtedly be a promising area as methods for bioengineering and pathogen biocontrol become amenable for rickettsiae.

Objective: Cystic biliary atresia (CBA) is a rare and peculiar type of biliary atresia (BA) that is easily confused with infantile choledochal cysts (CCs). This study explored information for early CBA diagnosis and treatment., Method: The authors retrospectively analyzed the clinical data of 32 children with hilar cysts from January 2013 to May 2021. According to the diagnosis, they were divided into the CBA ( n = 12) and CC ( n = 20) groups. Patient features, biochemical indexes, preoperative ultrasound characteristics, cholangiography features, and intraoperative findings were analyzed and compared between the two groups., Results: The alanine aminotransferase, aspartate aminotransferase, total bilirubin, and direct bilirubin levels in the CBA group were higher than in the CCs group ( P < 0.05). Additionally, B-mode ultrasound showed a cystic mass in front of the hepatic hilum, and the cyst size was much smaller in the CBA group compared with the CC group (2.2 ± 1.3 cm vs. 6.0 ± 2.2 cm, P < 0.001). Among all of the parameters, cyst width was the most accurate for identifying CBA and CCs. A cutoff value of 2.5 cm (area under the curve, 0.98, P < 0.001) showed 90.9% sensitivity and 95% specificity for cyst size., Conclusion: For children with early-onset severe jaundice, and if the width of the cystic mass was ≤2.5 cm, a diagnosis of CBA was highly likely. Early cholangiography and surgical treatment are necessary for the effective treatment of these infants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Gao, Zheng, Huang, Du, Zhu, Liu and Jin.)

Introduction and Hypothesis: The efficacy of physiotherapy for postpartum lower urinary tract symptoms (LUTS) has attracted considerable research interest. In the current study we evaluated the efficacy and safety of pelvic floor muscle training (PFMT) combined with biofeedback (BF), electrical stimulation (ES) therapy, or both for postpartum LUTS., Methods: PUBMED, EMBASE, Web of Science, Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Chinese Science and Technique Journals Database, and Wanfang databases were searched from inception to December 2020. Eligible randomized controlled trials on postpartum LUTS comparing PFMT plus BF, ES, or both with PFMT alone were included. The Cochrane handbook was used to evaluate the quality of the studies., Results: Seventeen studies were included. The results of the meta-analysis showed that PFMT plus ES with or without BF was more effective than PFMT alone. Patients receiving PFMT plus ES and BF achieved greater improvement than controls receiving PFMT alone in incontinence quality of life scores (mean difference: 15.33, 95% confidence interval [CI]: 11.70-18.97, P < 0.00001), pelvic floor muscle strength (risk ratio: 2.29, 95% CI: 1.53-3.43, P < 0.0001), and urodynamic parameters (maximum urethral closure pressure, abdominal leak point pressure, and maximum urinary flow rate), and 1-h urine leakage (standardized mean difference: -0.70, 95% CI: -1.23 to -0.17, P = 0.010) also decreased., Conclusions: PFMT plus ES with or without BF exhibited better efficacy and safety for early postpartum LUTS than PFMT alone., (© 2021. The International Urogynecological Association.)

Abdominal aortic aneurysm (AAA) is a localized enlargement of the abdominal aorta, such that the diameter exceeds 3 cm. The natural history of AAA is progressive growth leading to rupture, an event that carries up to 90% risk of mortality. Hence there is a need to predict the growth of the diameter of the aorta based on the diameter of a patient's aneurysm at initial screening and aided by non-invasive biomarkers. IL-6 is overexpressed in AAA and was suggested as a prognostic marker for the risk in AAA. The present paper develops a mathematical model which relates the growth of the abdominal aorta to the serum concentration of IL-6. Given the initial diameter of the aorta and the serum concentration of IL-6, the model predicts the growth of the diameter at subsequent times. Such a prediction can provide guidance to how closely the patient's abdominal aorta should be monitored. The mathematical model is represented by a system of partial differential equations taking place in the aortic wall, where the media is assumed to have the constituency of an hyperelastic material.

To explore the possibility of using chemical extraction methods to predict phytoavailability/bioaccumulation of soil-bound MeHg, MeHg extractions by three widely-used extractants (CaCl2, DTPA, and (NH4)2S2O3) were compared with MeHg accumulation in rice grains. Despite of variations in characteristics of different soils, MeHg extracted by (NH4)2S2O3 (highly affinitive to MeHg) correlated well with grain MeHg levels. Thus (NH4)2S2O3 extraction, solubilizing not only weakly-bound and but also strongly-bound MeHg, may provide a measure of 'phytoavailable MeHg pool' for rice plants. Besides, a better prediction of grain MeHg levels was obtained when growing condition of rice plants was also considered. However, MeHg extracted by CaCl2 or DTPA, possibly quantifying 'exchangeable MeHg pool' or 'weakly-complexed MeHg pool' in soils, may not indicate phytoavailable MeHg or predict grain MeHg levels. Our results provided the possibility of predicting MeHg phytoavailability/bioaccumulation by (NH4)2S2O3 extraction, which could be useful in screening soils for rice cultivation in contaminated areas., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Previous studies showed that Math1 homologous to human Hath1 can cause mouse goblet cells to differentiate. In this context it is important that the majority of colon cancers have few goblet cells. In the present study, the potential role of Hath1 in colon carcinogenesis was investigated. Sections of paraffin-embedded tissues were used to investigate the goblet cell population of normal colon mucosa, mucosa adjacent colon cancer and colon cancer samples from 48 patients. Hath1 and Muc2 expression in these samples were tested by immunohistochemistry, quantitative real-time reverse transcription -PCR and Western blotting. After the recombinant plasmid, pcDNA3.1(+)-Hath1 had been transfected into HT29 colon cancer cells, three clones were selected randomly to test the levels of Hath1 mRNA, Muc2 mRNA, Hath1, Muc2, cyclin D1 and p27 by quantitative real-time reverse transcription-PCR and Western blotting. Moreover, the proliferative ability of HT29 cells introduced with Hath1 was assessed by means of colony formation assay and xenografting. Expression of Hath1, Muc2, cyclin D1 and p27 in the xenograft tumors was also detected by Western blotting. No goblet cells were to be found in colon cancer and levels of Hath1 mRNA and Hath1, Muc2 mRNA and Muc2 were significantly down-regulated. Hath1 could decrease cyclin D1, increase p27 and Muc2 in HT29 cells and inhibit their proliferation. Hath1 may be an anti-oncogene in colon carcinogenesis.

Objective: To study the effect of Hath1 gene transfer on the proliferation of colonic cancer cells in vitro., Methods: The recombinant plasmid pcDNA3.1(+)-Hath1 was transfected into HT29 colonic cancer cells, and 3 positive cell clones were randomly selected to test the levels of Hath1 mRNA, Muc2 mRNA, Hath1, Muc2, cyclin D1 and p27 by quantitative real-time RT-PCR and Western blotting. The proliferation of the transfected HT29 cells was observed by means of colony formation assay and xenograft growth in nude mice., Results: Hath1 significantly down-regulated of cyclin D1 and up-regulate of p27 expressions and inhibited the proliferation of HT29 cells., Conclusion: Hath1 gene may be an anti-oncogene in colon carcinogenesis.