Skin infectome of patients with a tick bite history.

Introduction: Ticks are the most important obligate blood-feeding vectors of human pathogens. With the advance of high-throughput sequencing, more and more bacterial community and virome in tick has been reported, which seems to pose a great threat to people. Methods: A total of 14 skin specimens collected from tick-bite patients with mild to severe symptoms were analyzed through meta-transcriptomic sequencings. Results: Four bacteria genera were both detected in the skins and ticks, including Pseudomonas, Acinetobacter, Corynebacterium and Propionibacterium, and three tick-associated viruses, Jingmen tick virus (JMTV), Bole tick virus 4 (BLTV4) and Deer tick mononegavirales-like virus (DTMV) were identified in the skin samples. Except of known pathogens such as pathogenic rickettsia, Coxiella burnetii and JMTV, we suggest Roseomonas cervicalis and BLTV4 as potential new agents amplified in the skins and then disseminated into the blood. As early as 1 day after a tick-bite, these pathogens can transmit to skins and at most four ones can co-infect in skins. Discussion: Advances in sequencing technologies have revealed that the diversity of tick microbiome and virome goes far beyond our previous understanding. This report not only identifies three new potential pathogens in humans but also shows that the skin barrier is vital in preventing horizontal transmissions of tick-associated bacteria or virus communities to the host. It is the first research on patients' skin infectome after a tick bite and demonstrates that more attention should be paid to the cutaneous response to prevent tick-borne illness.

A Generative Image Inpainting Model Based on Edge and Feature Self-Arrangement Constraints.

At present, the image inpainting method based on deep learning has achieved a better inpainting effect than traditional methods, but the inpainting results still have problems such as local structure disorder and blurred texture when the images involving a large defect area are processed. This paper proposes a second-order generative image inpainting model based on edge and feature self-arrangement constraints. The model consists of two parts: edge repair network and image repair network. Based on the self-encoder, the edge repair network generates the edges in the defect area according to the known information of the image and improves the edge repair effect by minimizing the adversarial loss and feature matching loss. The image inpainting network fills the defect area with the edge repair result as a priori condition. On the basis of U-Net, the feature self-arrangement module (FSM) is proposed to reconstruct the coding features of a specific scale, and the reconstructed feature skips to connect the decoding layer of the same scale, and it is fused with the upper layer underlying features for decoding. Meanwhile, guide loss, adversarial loss, and reconstruction loss are introduced to narrow the difference between the repaired image and the original image. The experimental results show that the inpainting results of the proposed model have stronger structural connectivity and clearer textures and the performance of PSNR, SSIM, and mean L1 loss in the Celeba, Facade, and Places2 is better than other inpainting methods, indicating that the algorithm can produce an inpainting effect with highly connected structure, reasonable semantics, and fine details.

Four plasma membrane-localized MGR transporters mediate xylem Mg2+ loading for root-to-shoot Mg2+ translocation in Arabidopsis.

Magnesium (Mg2+), an essential structural component of chlorophyll, is absorbed from the soil by roots and transported to shoots to support photosynthesis in plants. However, the molecular mechanisms underlying root-to-shoot Mg2+ translocation remain largely unknown. We describe here the identification of four plasma membrane (PM)-localized transporters, named Mg2+ release transporters (MGRs), that are critical for root-to-shoot Mg transport in Arabidopsis. Functional complementation assays in a Mg2+-uptake-deficient bacterial strain confirmed that these MGRs conduct Mg2+ transport. PM-localized MGRs (MGR4, MGR5, MGR6, and MGR7) were expressed primarily in root stellar cells and participated in the xylem loading step of the long-distance Mg2+ transport process. In particular, MGR4 and MGR6 played a major role in shoot Mg homeostasis, as their loss-of-function mutants were hypersensitive to low Mg2+ but tolerant to high Mg2+ conditions. Reciprocal grafting analysis further demonstrated that MGR4 functions in the root to determine shoot Mg2+ accumulation and physiological phenotypes caused by both low- and high-Mg2+ stress. Taken together, our study has identified the long-sought transporters responsible for root-to-shoot Mg2+ translocation in plants.

Tale of Three Phosphate Additives for Stabilizing NCM811/Graphite Pouch Cells: Significance of Molecular Structure-Reactivity in Dictating Interphases and Cell Performance.

Electrolyte additives have been extensively used as an economical approach to improve Li-ion battery (LIB) performances; however, their selection has been conducted on an Edisonian trial-and-error basis, with little knowledge about the relationship between their molecular structure and reactivity as well as the electrochemical performance. In this work, a series of phosphate additives with systematic structural variation were introduced with the purpose of revealing the significance of additive structure in building a robust interphase and electrochemical property in LIBs. By comparing the interphases formed by tripropyl phosphate (TPPC1), triallyl phosphate (TPPC2), and tripropargyl phosphate (TPPC3) containing alkane, alkene, and alkyne functionalities, respectively, theoretical calculations and comprehensive characterizations reveal that TPPC3 and TPPC2 exhibit more reactivity than TPPC1, and both can preferentially decompose both reductively and oxidatively, forming dense and protective interphases on both the cathode and anode, but they lead to different long-term cycling behaviors at 55 °C. We herein correlate the electrochemical performance of the high energy Li-ion cells to the molecular structure of these additives, and it is found that the effectiveness of TPPC1, TPPC2, and TPPC3 in preventing gas generation, suppressing interfacial resistance growth, and improving cycling stability can be described as TPPC3 > TPPC2 > TPPC1, i.e., the most unsaturated additive TPPC3 is the most effective additive among them. The established correlation between structure-reactivity and interphase-performance will doubtlessly construct the principle foundation for the rational design of new electrolyte components for future battery chemistry.

Virome and Blood Meal-Associated Host Responses in Ixodes persulcatus Naturally Fed on Patients.

The long-lasting co-evolution of ticks with pathogens results in mutual adaptation. Blood-feeding is one of the critical physiological behaviors that have been associated with the tick microbiome; however, most knowledge was gained through the study of laboratory-reared ticks. Here we detached Ixodes persulcatus ticks at different stages of blood-feeding from human patients and performed high-throughput transcriptomic analysis on them to identify their virome and genes differentially expressed between flat and fully fed ticks. We also traced bloodmeal sources of those ticks and identified bats and three other potential mammalian hosts, highlighting the public health significance. We found Jingmen tick virus and 13 putative new viruses belonging to 11 viral families, three of which even exhibited high genetic divergence from viruses previously reported in the same tick species from the same geographic region. Furthermore, differential expression analysis suggested a downregulation of antioxidant genes in the fully fed I. persulcatus ticks, which might be related to bloodmeal-related redox homeostasis. Our work highlights the significance of active surveillance of tick viromes and suggests a role of reactive oxygen species (ROS) in modulating changes in the microbiome during blood-feeding.

Analysis of regional economic development based on land use and land cover change information derived from Landsat imagery.

The monitoring of economic activities is of great significance for understanding regional economic development level and policymaking. As the carrier of economic activities, land resource is an indispensable production factor of economic development, and economic growth leads to increased demand for land as well as changes in land utilization form. As an important means of earth observation, remote-sensing technology can obtain the information of land use and land cover change (LUCC) related to economic activities. This study proposes a method for analysing regional economic situations based on remote-sensing technology, from which LUCC information extraction, sensitivity factor selection, model construction and accuracy evaluation were implemented. This approach was validated with experiments in Zhoushan City, China. The results show that the economic statistical index is most sensitive to the construction land area, and the average correlation coefficient between the actual data and the predicted data is 0.949, and the average of mean relative error is 14.21%. Therefore, this paper suggests that LUCC could be utilised as an explanatory indicator for estimating economic development at the regional level, and the potential applications of remotely-sensed image in economic activity monitoring are worth pursuing.

Human Case Infected With Babesia venatorum: A 5-Year Follow-Up Study.

BACKGROUND: Human babesiosis is a common zoonosis caused by Babesia and is attracting an increasing concern worldwide. The natural course of babesiosis infection and how the human immune system changes during the course of babesiosis infection are not clear. METHODS: We followed up 1 case infected with Babesia venatorum for 5 years. The patient was immune-intact and received no standard treatment. Clinical data were obtained from medical records. Microbiological tests, ribonucleic acid (RNA) sequence, and serum cytokines and chemokines were detected at different time points. RESULTS: The patient was confirmed as B venatorum infection based on his tick-bite history, clinical manifestations, and positive results of microbiological tests. The parasitemia of the patient persisted for approximately 2 months. With flu-like symptoms aggravating, most cytokines and chemokines in RNA and protein levels increased progressively and reached the peak when fever occurred; and their concentrations decreased to baseline during the same time as clearance of babesia parasites. CONCLUSIONS: Babesia venatorum infection could take a mild self-limited course in immune-intact individuals. The natural changes of most cytokines and chemokines demonstrated very similar trends, which correlated with blood parasitemia and clinical manifestations. Cytokine profiles involving multiple inflammatory cytokines might be a good indicator of babesia infection.

Cutaneous Immunoprofiles of Three Spotted Fever Group Rickettsia Cases.

Spotted fever group rickettsia (SFGR) can cause mild to fatal illness. The early interaction between the host and rickettsia in skin is largely unknown, and the pathogenesis of severe rickettsiosis remains an important topic. A surveillance of SFGR infection by PCR of blood and skin biopsy specimens followed by sequencing and immunohistochemical (IHC) detection was performed on patients with a recent tick bite between 2013 and 2016. Humoral and cutaneous immunoprofiles were evaluated in different SFGR cases by serum cytokine and chemokine detection, skin IHC staining, and transcriptome sequencing (RNA-seq). A total of 111 SFGR cases were identified, including 79 "Candidatus Rickettsia tarasevichiae," 22 Rickettsia raoultii, 8 Rickettsia sibirica, and 2 Rickettsia heilongjiangensis cases. The sensitivity to detect SFGR in skin biopsy specimens (9/24, 37.5%) was significantly higher than that in blood samples (105/2,671, 3.9%) (P < 0.05). As early as 1 day after the tick bite, rickettsiae could be detected in the skin. R. sibirica infection was more severe than "Ca Rickettsia" and R. raoultii infections. Increased levels of serum interleukin-18 (IL-18), IP10, and monokine induced by gamma interferon (MIG) and decreased levels of IL-2 were observed in febrile patients infected with R. sibirica compared to those infected with "Ca Rickettsia." RNA-seq and IHC staining could not discriminate between SFGR-infected and uninfected tick bite skin lesions. However, the type I interferon (IFN) response was differently expressed between R. sibirica and R. raoultii infections at the cutaneous interface. It is concluded that skin biopsy specimens were more reliable for the detection of SFGR infection in human patients although the immunoprofile may be complicated by immunomodulators induced by the tick bite.

Rice transcription factor OsMADS57 regulates plant height by modulating gibberellin catabolism.

BACKGROUND: The MADS-box transcription factors mainly function in floral organ organogenesis and identity specification. Few research on their roles in vegetative growth has been reported. RESULTS: Here we investigated the functions of OsMADS57 in plant vegetative growth in rice (Oryza sativa). Knockdown of OsMADS57 reduced the plant height, internode elongation and panicle exsertion in rice plants. Further study showed that the cell length was remarkably reduced in the uppermost internode in OsMADS57 knockdown plants at maturity. Moreover, OsMADS57 knockdown plants were more sensitive to gibberellic acid (GA3), and contained less bioactive GA3 than wild-type plants, which implied that OsMADS57 is involved in gibberellin (GA) pathway. Expectedly, the transcript levels of OsGA2ox3, encoding GAs deactivated enzyme, were significantly enhanced in OsMADS57 knockdown plants. The level of EUI1 transcripts involved in GA deactivation was also increased in OsMADS57 knockdown plants. More importantly, dual-luciferase reporter assay and electrophoretic mobility shift assay showed that OsMADS57 directly regulates the transcription of OsGA2ox3 as well as EUI1 through binding to the CArG-box motifs in their promoter regions. In addition, OsMADS57 also modulated the expression of multiple genes involved in GA metabolism or GA signaling pathway, indicating the key and complex regulatory role of OsMADS57 in GA pathway in rice. CONCLUSIONS: These results indicated that OsMADS57 acts as an important transcriptional regulator that regulates stem elongation and panicle exsertion in rice via GA-mediated regulatory pathway.

Emergence of human infection with Jingmen tick virus in China: A retrospective study.

BACKGROUND: A tick-borne segmented RNA virus called Jingmen tick virus (JMTV) was recently identified, variants of which were detected in a non-human primate host and fatal patients with Crimean-Congo haemorrhagic fever. We investigated its infectivity and pathogenicity for humans. METHODS: We obtained skin-biopsy, blood and serum samples from patients with tick bites, and used high-throughput sequencing, in situ hybridisation, and serologic testing to diagnose and ascertain the cases of JMTV infection. FINDINGS: A JMTV strain was isolated from the tick Amblyomma javanense into an embryo-derived tick cell line. We obtained sustained passage of JMTV, and revealed that it was able to accumulate in salivary glands of experimentally infected ticks. Four JMTV-infected patients were identified by high-throughput sequencing of skin biopsies and blood samples. The virus replication in skin tissue was visualised by in situ hybridisation. The four patients all had an itchy or painful eschar at the site of tick bite, with or without lymphadenopathy. Immunohistochemical examination revealed remarkable local inflammation manifested as infiltration by neutrophils. Eight patients were identified by serological testing and showed more severe clinical manifestations. Two Ixodes persulcatus ticks detached from patients were positive for JMTV. All JMTV strains identified in this study formed a well-supported sub-lineage, distinct from those previously reported in China. Interpretation The public significance of JMTV should be highly concerning due to its potential pathogenicity for humans and efficient transmission by potential ticks. FUND: China Natural Science Foundation, State Key Research Development Programme, and United Kingdom Biotechnology and Biological Sciences Research Council.

OsMADS27 regulates the root development in a NO3--Dependent manner and modulates the salt tolerance in rice (Oryza sativa L.).

OsMADS27 is one of the ANR1-like homologues in rice, whreas its functions in plant growth and development as well as the abiotic stress responses remain unclear. Here we investigated the roles of OsMADS27 in the root development in response to NO3- availability. Constitutive expression of OsMADS27 significantly inhibited the elongation of primary root (PR), but enhanced lateral root (LR) formation in a NO3--dependent manner. Furthermore, OsMADS27 overexpression promoted NO3- accumulation as well as the expression of NO3- transporter genes. ABA is reported to play an important role in mediating the effects of NO3- on the root development, thus it is supposed that OsMADS27 might regulate the root growth and development by ABA pathway. The root growth and development in OsMADS27 overexpression lines was shown to be more sensitive to exogenous ABA than wild type. Moreover, under NO3- conditions, higher levels of ABA accumulates in OsMADS27 overexpression plants. Yeast two-hybrid and bimolecular fluorescence complementation (BiFC) assays showed that OsMADS27 physically interacts with ABA-INSENSITIVE5 (OsABI5) via DELLA protein OsSLR1. More importantly, OsMADS27 overexpression could enhance the salt tolerance. Taken together, our findings suggested that OsMADS27 is an important regulator controlling the root system development and adaption to osmotic stress in rice.

Rice transcription factor OsMADS25 modulates root growth and confers salinity tolerance via the ABA-mediated regulatory pathway and ROS scavenging.

Plant roots are constantly exposed to a variety of abiotic stresses, and high salinity is one of the major limiting conditions that impose constraints on plant growth. In this study, we describe that OsMADS25 is required for the root growth as well as salinity tolerance, via maintaining ROS homeostasis in rice (Oryza sativa). Overexpression of OsMADS25 remarkably enhanced the primary root (PR) length and lateral root (LR) density, whereas RNAi silence of this gene reduced PR elongation significantly, with altered ROS accumulation in the root tip. Transcriptional activation assays indicated that OsMADS25 activates OsGST4 (glutathione S-transferase) expression directly by binding to its promoter. Meanwhile, osgst4 mutant exhibited repressed growth and high sensitivity to salinity and oxidative stress, and recombinant OsGST4 protein was found to have ROS-scavenging activity in vitro. Expectedly, overexpression of OsMADS25 significantly enhanced the tolerance to salinity and oxidative stress in rice plants, with the elevated activity of antioxidant enzymes, increased accumulation of osmoprotective solute proline and reduced frequency of open stoma. Furthermore, OsMADS25 specifically activated the transcription of OsP5CR, a key component of proline biosynthesis, by binding to its promoter. Interestingly, overexpression of OsMADS25 raised the root sensitivity to exogenous ABA, and the expression of ABA-dependent stress-responsive genes was elevated greatly in overexpression plants under salinity stress. In addition, OsMADS25 seemed to promote auxin signaling by activating OsYUC4 transcription. Taken together, our findings reveal that OsMADS25 might be an important transcriptional regulator that regulates the root growth and confers salinity tolerance in rice via the ABA-mediated regulatory pathway and ROS scavenging.

Overexpression of RCc3 improves root system architecture and enhances salt tolerance in rice.

Root system architecture represents an underexplored target for improving global crop yields. In this study, we investigated the biological role of the rice root-specific gene RCc3 in improving root growth and responses to abiotic stress by overexpressing RCc3 in rice plants. RCc3 was induced by osmotic and heat stress. RCc3 overexpression produced pleiotropic phenotypes of improved root system architecture, including increased growth of primary root, adventitious roots and lateral roots at the seedling stage. Further study indicated that auxin accumulation in the root was increased through auxin local biosynthesis and polar auxin transport in RCc3 overexpression lines. At maturity, the plant height and panicle traits were also significantly enhanced in overexpression plants. Under osmotic and heat stress conditions, the root and shoot growth were less severely inhibited in RCc3 overexpressing transgenic plants than that in wild-type plants, and the transcript levels of abiotic stress-related genes were significantly increased. Moreover, overexpression of RCc3 remarkably enhanced the tolerance to salt stress, with the elevated activities of antioxidant enzymes. Taken together, the data showed that RCc3 overexpression can improve rice root system, promote plant growth, and enhance plant tolerance to salt stress.

Human Babesiosis Caused by a Babesia crassa-Like Pathogen: A Case Series.

Background: Human babesiosis is an emerging health problem in China. Methods: Babesia were identified in ticks, sheep, and humans in northeastern China using polymerase chain reaction (PCR) followed by genetic sequencing. We enrolled residents who experienced a viral-like illness after recent tick bite or were healthy residents. We defined a case using the definition for babesiosis developed by the US Centers for Disease Control and Prevention. Results: A Babesia crassa-like agent was identified in Ixodes persulcatus and Haemaphysalis concinna ticks using PCR followed by sequencing. The agent was characterized through phylogenetic analyses of the 18S rRNA gene, the ß-tubulin gene, and the internal transcribed spacer region. We tested sheep as a possible reservoir and found that 1.1% were infected with the B. crassa-like agent. We screened 1125 human participants following tick bites using B. crassa-specific PCR and identified 31 confirmed and 27 suspected cases. All the patients were previously healthy except for 1 with an ovarian tumor. Headache (74%), nausea or vomiting (52%), and fever (48%) were the most common clinical manifestations of confirmed cases. Six of 10 cases remained PCR positive for B. crassa-like infection 9 months after initial diagnosis. Asymptomatic infections were detected in 7.5% of 160 local residents. Conclusions: We identified B. crassa-like infection in people in northeastern China that caused mild to moderate symptoms. The possibility of more severe disease in immunocompromised patients and of transmission through the blood supply due to asymptomatic infections justifies further investigation of this reported infection.

Borrelia miyamotoi Infections in Humans and Ticks, Northeastern China.

We conducted an investigation of Borrelia miyamotoi infections in humans and ticks in northeastern China. Of 984 patients reporting recent tick bites, 14 (1.4%) were found to be infected with B. miyamotoi by PCR and genomic sequencing. The 14 patients had nonspecific febrile manifestations, including fever, headache, anorexia, asthenia, and arthralgia. Rash, eschar, and regional lymphadenopathy were each observed in 1 patient. Four (28.6%) patients were hospitalized because of severe disease. B. miyamotoi was detected in 3.0% (19/627) of Ixodes persulcatus, 1 (2.8%) of 36 Haemaphysalis concinna, and none of 29 Dermacentor silvarum ticks. Phylogenetic analyses based on sequences of a nearly entire 16s rRNA gene, a partial flagellin gene, and the glycerophosphodiester phosphodiesterase gene revealed that B. miyamotoi identified in patients and ticks were clustered in the group of the Siberian type. These findings indicate that B. miyamotoi is endemic in northeastern China and its public health significance deserves further investigation.

Human infection with a novel tick-borne Anaplasma species in China: a surveillance study.

BACKGROUND: Anaplasma phagocytophilum and Anaplasma ovis cause human infections. We investigated the potential for human pathogenicity of a newly discovered Anaplasma species infecting goats in China. METHODS: We collected blood samples from patients with a history of tick bite in the preceding 2 months at Mudanjiang Forestry Central Hospital of Heilongjiang Province from May 1, to June 10, 2014, to detect the novel Anaplasma species by PCR. We inoculated positive samples into cell cultures. We characterised the isolated pathogen by morphological and phylogenetic analyses. We tested serum antibodies by indirect immunofluorescence assay. FINDINGS: 28 (6%) of 477 patients assessed were infected with the novel Anaplasma species according to PCR and sequencing. We isolated the pathogen in vitro from three patients. Phylogenetic analyses of rrs, gltA, groEL, msp2, and msp4 showed that the pathogen was distinct from all known Anaplasma species. We provisionally nominate it "Anaplasma capra". 22 (92%) of 24 patients with data available had seroconversion or a four-fold increase in antibody titres. All 28 patients developed non-specific febrile manifestations, including fever in 23 (82%), headache in 14 (50%), malaise in 13 (46%), dizziness in nine (32%), myalgia in four (14%), and chills in four (14%). Additionally, ten (36%) of 28 patients had rash or eschar, eight (29%) had lymphadenopathy, eight (29%) had gastrointestinal symptoms, and three (11%) had stiff neck. Five patients were admitted to hospital because of severe disease. Six (35%) of 17 patients with data available had high hepatic aminotransferase concentrations. INTERPRETATION: The emergence of "A capra" as a cause of human disease suggests that individuals living in or travelling to endemic regions in northern China should take precautions to reduce their risk of exposure to this novel tick-borne pathogen. FUNDING: Natural Science Foundation of China and the US National Institutes of Health.

Epidemiological, clinical, and laboratory characteristics of 48 cases of "Babesia venatorum" infection in China: a descriptive study.

BACKGROUND: Human babesiosis is an emerging zoonosis. "Babesia venatorum" has been identified in only four asplenic men and a child so far. We aimed to describe the epidemiological, clinical, and laboratory characteristics of a series of cases with "B venatorum" infection identified in a sentinel hospital in China. METHODS: We recruited participants with a recent tick bite at Mudanjiang Forestry Central Hospital, Heilongjiang province, China. Cases were diagnosed through PCR followed by sequencing, microscopic identification, or isolation by animal inoculation, or both. FINDINGS: 48 individuals (30 women or girls; median age 45 years, range 7 months to 75 years) with "B venatorum" infection were identified. 32 of these individuals were confirmed cases and 16 were probable cases. None of the 48 cases had received a blood transfusion or had a splenectomy. Geographically, cases were distributed diffusely throughout the hospital catchment area. Of the 32 confirmed cases, 21 (66%) presented with a fever, 13 (41%) with a headache, 12 (38%) with myalgia or arthralgia, and three (9%) with chills. 14 (44%) patients had fatigue, eight (25%) had dizziness, and eight (25%) had hypersomnia. Six (19%) patients had an erythematous non-pruritic rash around the tick-bite site and two (6%) had lymphadenopathy. Seven (22%) and four (13%) patients had anaemia and thrombocytopenia, respectively, and seven (50%) of 14 patients with confirmed infection had increased hepatic transaminase concentrations. In the confirmed cases, concentrations of intercellular adhesion molecule 3 (p<0·001), P-selectin (p<0·05), and platelet endothelial cell adhesion molecule 1 (p<0·001) were significantly reduced, whereas tumour necrosis factor α (p<0·01) and vascular cell adhesion molecule 1 (p<0·001) were significantly increased. INTERPRETATION: "B venatorum" infection should be included in the differential diagnosis of patients with a tick-exposure history in areas where this pathogen has previously been identified in ticks or people. FUNDING: Natural Science Foundation of China and Mega-Project for Infectious Diseases.

Human infections with Rickettsia raoultii, China.

We used molecular methods to identify Rickettsia raoultii infections in 2 persons in China. These persons had localized rashes around sites of tick bites. R. raoultii DNA was detected in 4% of Dermacentor silvarum ticks collected in the same area of China and in 1 feeding tick detached from 1 patient.