Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins.

The current outbreak of coronavirus disease-2019 (COVID-19) poses unprecedented challenges to global health1. The new coronavirus responsible for this outbreak-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-shares high sequence identity to SARS-CoV and a bat coronavirus, RaTG132. Although bats may be the reservoir host for a variety of coronaviruses3,4, it remains unknown whether SARS-CoV-2 has additional host species. Here we show that a coronavirus, which we name pangolin-CoV, isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively. In particular, the receptor-binding domain of the S protein of pangolin-CoV is almost identical to that of SARS-CoV-2, with one difference in a noncritical amino acid. Our comparative genomic analysis suggests that SARS-CoV-2 may have originated in the recombination of a virus similar to pangolin-CoV with one similar to RaTG13. Pangolin-CoV was detected in 17 out of the 25 Malayan pangolins that we analysed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus from pangolins that is closely related to SARS-CoV-2 suggests that these animals have the potential to act as an intermediate host of SARS-CoV-2. This newly identified coronavirus from pangolins-the most-trafficked mammal in the illegal wildlife trade-could represent a future threat to public health if wildlife trade is not effectively controlled.

Pathogenicity, tissue tropism and potential vertical transmission of SARSr-CoV-2 in Malayan pangolins.

Malayan pangolin SARS-CoV-2-related coronavirus (SARSr-CoV-2) is closely related to SARS-CoV-2. However, little is known about its pathogenicity in pangolins. Using CT scans we show that SARSr-CoV-2 positive Malayan pangolins are characterized by bilateral ground-glass opacities in lungs in a similar manner to COVID-19 patients. Histological examination and blood gas tests are indicative of dyspnea. SARSr-CoV-2 infected multiple organs in pangolins, with the lungs the major target, and histological expression data revealed that ACE2 and TMPRSS2 were co-expressed with viral RNA. Transcriptome analysis indicated that virus-positive pangolins were likely to have inadequate interferon responses, with relative greater cytokine and chemokine activity in the lung and spleen. Notably, both viral RNA and viral proteins were detected in three pangolin fetuses, providing initial evidence for vertical virus transmission. In sum, our study outlines the biological framework of SARSr-CoV-2 in pangolins, revealing striking similarities to COVID-19 in humans.

Metabolic flexibilities and vulnerabilities in the pentose phosphate pathway of the zoonotic pathogen Toxoplasma gondii.

Metabolic pathways underpin the growth and virulence of intracellular parasites and are therefore promising antiparasitic targets. The pentose phosphate pathway (PPP) is vital in most organisms, providing a reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) and ribose sugar for nucleotide synthesis; however, it has not yet been studied in Toxoplasma gondii, a widespread intracellular pathogen and a model protozoan organism. Herein, we show that T. gondii has a functional PPP distributed in the cytoplasm and nucleus of its acutely-infectious tachyzoite stage. We produced eight parasite mutants disrupting seven enzymes of the PPP in T. gondii. Our data show that of the seven PPP proteins, the two glucose-6-phosphate dehydrogenases (TgG6PDH1, TgG6PDH2), one of the two 6-phosphogluconate dehydrogenases (Tg6PGDH1), ribulose-5-phosphate epimerase (TgRuPE) and transaldolase (TgTAL) are dispensable in vitro as well as in vivo, disclosing substantial metabolic plasticity in T. gondii. Among these, TgG6PDH2 plays a vital role in defense against oxidative stress by the pathogen. Further, we show that Tg6PGDH2 and ribulose-5-phosphate isomerase (TgRPI) are critical for tachyzoite growth. The depletion of TgRPI impairs the flux of glucose in central carbon pathways, and causes decreased expression of ribosomal, microneme and rhoptry proteins. In summary, our results demonstrate the physiological need of the PPP in T. gondii while unraveling metabolic flexibility and antiparasitic targets.

Mycoplasma genitalium membrane lipoprotein induces GAPDH malonylation in urethral epithelial cells to regulate cytokine response.

Membrane lipoproteins serve as primary pro-inflammatory virulence factors in Mycoplasma genitalium. Membrane lipoproteins primarily induce inflammatory responses by activating Toll-like Receptor 2 (TLR2); however, the role of the metabolic status of urethral epithelial cells in inflammatory response remains unclear. In this study, we found that treatment of uroepithelial cell lines with M. genitalium membrane lipoprotein induced metabolic reprogramming, characterized by increased aerobic glycolysis, decreased oxidative phosphorylation, and increased production of the metabolic intermediates acetyl-CoA and malonyl-CoA. The metabolic shift induced by membrane lipoproteins is reversible upon blocking MyD88 and TRAM. Malonyl-CoA induces malonylation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and malonylated GAPDH could dissociate from the 3' untranslated region of TNF-α and IFN-γ mRNA. This dissociation greatly reduces the inhibitory effect on the translation of TNF-α and IFN-γ mRNA, thus achieving fine-tuning control over cytokine secretion. These findings suggest that GAPDH malonylation following M. genitalium infection is an important inflammatory signal that plays a crucial role in urogenital inflammatory diseases.

Multifunctional 2-bit coded reconfigurable metasurface based on graphene-vanadium dioxide.

In this paper, a graphene-vanadium dioxide-based reconfigurable metasurface unit structure is proposed. Using the change at a graphene Fermi energy level on the surface of the unit structure to satisfy the 2-bit coding condition, four reflection units with a phase difference of 90 ∘ can be discovered. The modulating impact of the multi-beam reflection wave with 1-bit coding is then confirmed. Then we study the control of a single-beam reflected wave by metasurfaces combined with a convolution theorem in a 2-bit coding mode. Finally, when vanadium dioxide is in an insulating condition, the structure can also be transformed into a terahertz absorber. It is possible to switch between a reflection beam controller and a terahertz multifrequency absorber simply by changing the temperature of the vanadium dioxide layer without retooling a new metasurface. Moreover, compared with the 1-bit coded metasurface, it increases the ability of single-beam regulation, which makes the device more powerful for beam regulation.

Zoonotic Cryptosporidium and Giardia in marsupials-an update.

Marsupials, inhabiting diverse ecosystems, including urban and peri-urban regions in Australasia and the Americas, intersect with human activities, leading to zoonotic spill-over and anthroponotic spill-back of pathogens, including Cryptosporidium and Giardia. This review assesses the current knowledge on the diversity of Cryptosporidium and Giardia species in marsupials, focusing on the potential zoonotic risks. Cryptosporidium fayeri and C. macropodum are the dominant species in marsupials, while in possums, the host-specific possum genotype dominates. Of these three species/genotypes, only C. fayeri has been identified in two humans and the zoonotic risk is considered low. Generally, oocyst shedding in marsupials is low, further supporting a low transmission risk. However, there is some evidence of spill-back of C. hominis into kangaroo populations, which requires continued monitoring. Although C. hominis does not appear to be established in small marsupials like possums, comprehensive screening and analysis are essential for a better understanding of the prevalence and potential establishment of zoonotic Cryptosporidium species in small marsupials. Both host-specific and zoonotic Giardia species have been identified in marsupials. The dominance of zoonotic G. duodenalis assemblages A and B in marsupials may result from spill-back from livestock and humans and it is not yet understood if these are transient or established infections. Future studies using multilocus typing tools and whole-genome sequencing are required for a better understanding of the zoonotic risk from Giardia infections in marsupials. Moreover, much more extensive screening of a wider range of marsupial species, particularly in peri-urban areas, is required to provide a clearer understanding of the zoonotic risk of Cryptosporidium and Giardia in marsupials.

Molecular characterization of a novel Spiruromorpha species in wild Chinese pangolin by mitogenome sequence analysis.

Pangolins are susceptible to a variety of gastrointestinal nematodes due to their burrowing lifestyle and feeding habits, and few parasitic nematodes have been reported. Here, a Chinese pangolin with old wounds on its leg and tail was rescued from the Heyuan City, Guangdong Province. The cox1 and SSU rRNA of the worms from the intestine of the Chinese pangolin had the highest sequence identity of 89.58% and 97.95% to the species in the infraorder Spiruromorpha. The complete mitogenome of the worm was further assembled by next-generation sequencing, with a size of 13,708 bp and a GC content of 25.6%. The worm mitogenome had the highest sequence identity of 78.56% to that of Spirocerca lupi, sharing the same gene arrangement with S. lupi and some species in other families under Spiruromorpha. However, the mitogenome between the worm and S. lupi showed differences in codon usage of PCGs, sequences of NCR, and tRNA secondary structures. Phylogenetic analysis showed that the worm mitogenome was clustered with S. lupi in the family Thelaziidae to form a separate branch. However, it is still difficult to identify the worm in the family Thelaziidae because the species in the family Thelaziidae are confused, specifically S. lupi and Thelazia callipaeda in the family Thelaziidae were separated and grouped with species from other families. Thus, the parasitic nematode from the Chinese pangolin may be a novel species in Spiruromorpha and closely related to S. lupi. This study enriches the data on gastrointestinal nematodes in the Chinese pangolin.

Ultrasound diagnosis and treatment of branchial cleft cyst and preoperative management.

OBJECTIVE: The ultrasonic diagnosis of cervical and facial cystic masses, as well as cases of missed diagnosis and misdiagnosis, was examined, to improve the diagnosis of branchial cleft anomalies. METHODS: A retrospective analysis was conducted on 17 patients with branchial cleft cyst anomalies, including 11 males and 6 females, aged 12-53 years, with an average age of 33 ± 2 years, were unilateral single. All patients who underwent an ultrasound examination and image storage for retrospective analysis, and both longitudinal and transverse sections were scanned to observe the shape, size, boundary, peripheral relationship, and blood flow signal of the masses. All cases were examined with an enhanced CT scan, and pathological reports were generated. RESULTS: Among the 17 cases of branchial cleft anomalies, 15 cases were branchial cleft cysts, while one case involved fistula formation and one case involved sinus tract formation. Based on the type of branchial cleft, the first, second, and third cysts were classified in 4, 12, and 1 case, respectively. The sensitivity rate and specificity of ultrasonic diagnosis were 14/17 (82.4%) and 4/6 (66.7%), respectively. Ultrasonic characteristic analysis for the masses can be found in simple cystic masses or hypoechoic masses, most of them are of a regular shape and have a distinct boundary, and almost no blood flow signal. All patients who were misdiagnosed exhibited blood flow signals, including 1 patient with an abundant blood flow signal, 1 patient suspected of having ectopic thyroid with an abnormal function due to the rat-tail sign, 2 patients misdiagnosed as local inflammatory focus, and 1 patient misdiagnosed with tuberculous lymphadenitis. CONCLUSION: Ultrasound has a detection rate of up to 100% for cervical and facial masses, providing a fundamental determination of lesion characteristics and specific guidance for preoperative diagnosis. If the blood flow signals can be identified and carefully considered their peripheral relationship, the diagnostic rate can be improved.

Sympatric Recombination in Zoonotic Cryptosporidium Leads to Emergence of Populations with Modified Host Preference.

Genetic recombination plays a critical role in the emergence of pathogens with phenotypes such as drug resistance, virulence, and host adaptation. Here, we tested the hypothesis that recombination between sympatric ancestral populations leads to the emergence of divergent variants of the zoonotic parasite Cryptosporidium parvum with modified host ranges. Comparative genomic analyses of 101 isolates have identified seven subpopulations isolated by distance. They appear to be descendants of two ancestral populations, IIa in northwestern Europe and IId from southwestern Asia. Sympatric recombination in areas with both ancestral subtypes and subsequent selective sweeps have led to the emergence of new subpopulations with mosaic genomes and modified host preference. Subtelomeric genes could be involved in the adaptive selection of subpopulations, while copy number variations of genes encoding invasion-associated proteins are potentially associated with modified host ranges. These observations reveal ancestral origins of zoonotic C. parvum and suggest that pathogen import through modern animal farming might promote the emergence of divergent subpopulations of C. parvum with modified host preference.

ABO blood groups and nosocomial infection.

The timely identification of the high-risk groups for nosocomial infections (NIs) plays a vital role in its prevention and control. Therefore, it is crucial to investigate whether the ABO blood group is a risk factor for NI. In this study, patients with NI and non-infection were matched by the propensity score matching method and a logistic regression model was used to analyse the matched datasets. The study found that patients with the B&AB blood group were susceptible to Escherichia coli (OR = 1.783, p = 0.039); the A blood group were susceptible to Staphylococcus aureus (OR = 2.539, p = 0.019) and Pseudomonas aeruginosa (OR = 5.724, p = 0.003); the A&AB blood group were susceptible to Pseudomonas aeruginosa (OR = 4.061, p = 0.008); the AB blood group were vulnerable to urinary tract infection (OR = 13.672, p = 0.019); the B blood group were susceptible to skin and soft tissue infection (OR = 2.418, p = 0.016); and the B&AB blood group were vulnerable to deep incision infection (OR = 4.243, p = 0.043). Summarily, the patient's blood group is vital for identifying high-risk groups for NIs and developing targeted prevention and control measures for NIs.

Graphene electromagnetically induced transparent polarization-insensitive sensors in the mid-infrared frequency band.

In this paper, a polarization-insensitive sensor based on graphene electromagnetically induced transparency (EIT) is proposed. The device consists of two graphene orthogonal T-shaped structures. This T-shaped resonator produces transparent windows that largely overlap under x and y polarizations, and the results demonstrate its good polarization insensitivity. The device can accomplish detection performance with sensitivity higher than 4960 nm/RIU and figure of merit (FOM) greater than 11.4. Meanwhile, when the Fermi energy level of graphene changes from 0.5 to 0.8 eV, it enables arbitrary modulation of the operating frequency over a wide frequency range of about 4.5 terahertz in the mid-infrared band. Our work has the potential to significantly advance the area of biological molecular detection.

Detection of unusual Cryptosporidium parvum subtype in patients with gastrointestinal cancer in Egypt.

While the importance of cryptosporidiosis in immunocompromised persons is well known, the prevalence of Cryptosporidium spp. in cancer patients is not clear. The current study was designed to assess the occurrence and genetic characteristics of Cryptosporidium spp. in patients with gastrointestinal (GI) cancer in Egypt. Stool samples were collected from 100 patients with GI malignancies and 20 healthy individuals without any GI manifestations (control group). They were screened by microscopy and the immunochromatographic RIDA®QUICK Cryptosporidium kit. Subtyping of Cryptosporidium spp. was conducted by sequence analysis of the glycoprotein 60 (gp60) locus. Sociodemographic, environmental data and information on GI symptoms, cancer types, and clinical treatment were obtained via a questionnaire. By microscopy and RIDA®QUICK, only 7% (7/100) of GI cancer patients were positive for Cryptosporidium, compared with 40% (40/100) by gp60 nPCR. No positives were obtained from the control group. Male sex (P = 0.02) and younger age (P = 0.004) were major Cryptosporidium risk factors for infection. The occurrence of Cryptosporidium was also significantly more frequent (P = 0.003) in watery stool samples. Sequence analysis of the gp60 amplicons (~ 400 bp) identified a novel C. parvum subtype with nine TCA repeats and eleven ACATCA repeats. A formal subtype designation could not be made due to the short sequence length. More studies should be conducted to verify the common occurrence of this unusual C. parvum subtype and establish its genetic identity.

Molecular Epidemiology of Human Cryptosporidiosis in Low- and Middle-Income Countries.

Cryptosporidiosis is one of the most important causes of moderate to severe diarrhea and diarrhea-related mortality in children under 2 years of age in low- and middle-income countries. In recent decades, genotyping and subtyping tools have been used in epidemiological studies of human cryptosporidiosis. Results of these studies suggest that higher genetic diversity of Cryptosporidium spp. is present in humans in these countries at both species and subtype levels and that anthroponotic transmission plays a major role in human cryptosporidiosis. Cryptosporidium hominis is the most common Cryptosporidium species in humans in almost all the low- and middle-income countries examined, with five subtype families (namely, Ia, Ib, Id, Ie, and If) being commonly found in most regions. In addition, most Cryptosporidium parvum infections in these areas are caused by the anthroponotic IIc subtype family rather than the zoonotic IIa subtype family. There is geographic segregation in Cryptosporidium hominis subtypes, as revealed by multilocus subtyping. Concurrent and sequential infections with different Cryptosporidium species and subtypes are common, as immunity against reinfection and cross protection against different Cryptosporidium species are partial. Differences in clinical presentations have been observed among Cryptosporidium species and C. hominis subtypes. These observations suggest that WASH (water, sanitation, and hygiene)-based interventions should be implemented to prevent and control human cryptosporidiosis in low- and middle-income countries.

Design and prediction of PIT devices through deep learning.

Graphene material has excellent performance and unique variable carrier density characteristics, making it an excellent mid-infrared material. And deep learning makes it possible to quickly design mid-infrared band devices with good performance. A graphene nano-ring-symmetric sector-shaped disk array structure based on the PIT principle is proposed here for sensing. The influence of structural parameters and Fermi energy changes are studied. And its FOM (Figure Of Merit) can reach 28.7; the sensitivity is 574 cm-1 / RIU (Refractive Index Unit). At the same time, we designed a six-layer deep learning network that can predict structural parameters and curve predictions. When predicting structural parameters, its MAPE (Mean Absolute Percentage Error) converges to 0.5. In curve prediction, MSE (Mean Square Error) converges to 1.2. It shows that predictions can be made very well. This paper proposes a symmetrical sector disk array structure and a 6-layer deep learning network. And the deep neural network designed based on the device data has good prediction accuracy under the premise of ensuring the network is simple. This will lay a good foundation for future sensor design and device acceleration optimization design.

Seroprevalence and risk factors of Toxoplasma gondii in urban cats from China.

BACKGROUND: Toxoplasma gondii infects almost all warm-blooded animals, and cats play a crucial role in the epidemiology of T. gondii as the definitive host. Despite sporadic reports on the seroprevalence of T. gondii in domestic cats, systematic surveys are lacking and some regions remain in China uninvestigated. METHODS: A total of 1,521 serum samples were collected from 10 regions of China and analyzed by antibodies against T. gondii by ELISA with the purpose of identifying risk factors of T. gondii infection in cats across China and obtaining seroprevalence data from some previously uninvestigated areas. RESULTS: Antibodies to T. gondii were detected in 62 of 1,478 (4.2%) urban pet cats and in 9 of 43 (20.9%) stray cats. Among the regions examined, the prevalence was 13% in Sichuan, 12.8% in Chongqing, 6.4% in Hunan, 2.5% in Hubei and 0.9% in Guangdong. Additionally, this is the first report on the seroprevalence of T. gondii in urban pet cats from Qinghai (6.2%), Anhui (3.1%), Jiangxi (2.5%), Shaanxi (2.4%) and Ningxia (1.6%). The age and lifestyle (stray or pet) of cats were identified as the risk factors for seropositivity by multivariate analysis of the data. CONCLUSIONS: Our findings improve our understanding of seroprevalence and risk factors of T. gondii infection in cats across China, and provide useful information for the formulating of preventive and control measures against this widespread zoonotic parasite.

Broadband tunable coding metasurfaces based on a metal patch and graphene for beam control at the terahertz frequencies.

We present a broadband tunable coding metasurfaces structure using a cruciate metal patch and circular graphene on a multilayer substrate. By changing the Fermi level of the graphene, we can achieve obvious reflection phase variation to design multi-bit coding metasurfaces. In the research of 1-bit coding metasurfaces, we combine the advantages of graphene and copper to realize the real-time adjustment of the reflected waves in four broadband frequency bands. In this case, we can control the number of far-field reflected waves in the frequency range of 5.45-6.45 THz. Then, we create 2-bit and 3-bit coding modes on the basis of 1-bit coding metasurfaces to obtain a single beam of reflected waves. Finally, we use the convolution calculation to realize the real-time adjustment of the single beam reflection direction from 0° to 360° in the azimuthal plane. Research of the 2-bit and 3-bit coding modes also provides a way to control the number and direction of the reflected beam, specifically in the 1-bit coding mode. The present coding metasurfaces structure provides inspiration for the design of functional devices in future-oriented intelligent communication.

Programmable bandstop filter based on spoof surface plasmon polaritons.

Spoof surface plasmon polaritons (SSPPs) have been developed rapidly because of the advantages of strong field constraints, low inter-channel cross talk, and low loss. However, the functions of plasmonic devices made of traditional passive SSPPs are completely fixed and cannot reach reconfigurable capability once the devices are fabricated. For the current development status, it is an urgent issue to design a reconfigurable device to control SPP waves dynamically in real time. This paper proposes a dynamic reconfigurable bandstop filter by using the concept of programmable SSPPs. The filter has a significant regulation function in the wideband range from 4 GHz to 22 GHz. The center frequency, number, and bandwidth of the stop band can be reconstructed in real time by programming the bias voltage, and the transmission coefficient (S21) has good transmission performance of more than -3dB. The results show that the experimental processing test is close to the theoretical simulation results, which proves the feasibility of the designed device. The study extends the functional principles of information science and digital logic to the application of physical devices.

Dynamically tunable broadband absorber/reflector based on graphene and VO2 metamaterials.

We propose a difunctional tunable broadband absorber/reflector consisting of a periodic cross-shaped graphene array and a vanadium dioxide (VO2) layer. When VO2 reflects the properties of metal, the proposed dual-function device is used as a reflector; when VO2 reflects the nature of the dielectric, the difunctional device will be used as an absorber. The simulation results indicate that more than 90% absorption bandwidth can be available in the absorber in the frequency range of 56.1-59.0 THz, up to 100%. Moreover, over 80% absorption can be achieved over the frequency range of 88.5 to 90.2 THz. In addition, the bandwidth and absorption of the metamaterial absorber can be dynamically changed because of the Fermi energy level in graphene and the temperature tunability of VO2. The proposed device can be applied to manufacturing infrared spectrophotometers, on-dispersive infrared photometers, and Fourier transform infrared spectrometers. Therefore, it has potential application in the field of environmental monitoring.

Prevalence and genetic characterization of Enterocytozoon bieneusi in children in Northeast Egypt.

Enterocytozoon bieneusi is the most common microsporidia in humans worldwide, in addition to infecting a wide range of animals. However, there is limited information about this pathogen in children in Egypt. Here, we carried out a molecular epidemiological study of E. bieneusi in child care centers in three provinces in Egypt. Altogether, 585 fresh fecal samples were collected from children attending 18 child care centers in El-Dakahlia, El-Gharbia, and Damietta provinces in Northeast Egypt during March 2015 to April 2016. PCR and sequence analyses of the ribosomal internal transcribed spacer (ITS) were used to detect and genotype E. bieneusi. Twenty-seven fecal samples (4.6%, 27/585) were positive for E. bieneusi. Five genotypes were identified, including type IV (n = 13), Peru8 (n = 9), Peru6 (n = 2), Peru11 (n = 2), and D (n = 1). Phylogenetic analysis indicated that the five genotypes of E. bieneusi detected in this study were clustered into zoonotic group 1. These data provide important information on the prevalence and genetic diversity of E. bieneusi in children in this country. Further epidemiological studies should be conducted to elucidate the role of zoonotic transmission in human E. bieneusi infections.