Global Dynamics of Porcine Enteric Coronavirus PEDV Epidemiology, Evolution, and Transmission.

With a possible origin from bats, the alphacoronavirus Porcine epidemic diarrhea virus (PEDV) causes significant hazards and widespread epidemics in the swine population. However, the ecology, evolution, and spread of PEDV are still unclear. Here, from 149,869 fecal and intestinal tissue samples of pigs collected in an 11-year survey, we identified PEDV as the most dominant virus in diarrheal animals. Global whole genomic and evolutionary analyses of 672 PEDV strains revealed the fast-evolving PEDV genotype 2 (G2) strains as the main epidemic viruses worldwide, which seems to correlate with the use of G2-targeting vaccines. The evolving pattern of the G2 viruses presents geographic bias as they evolve tachytely in South Korea but undergo the highest recombination in China. Therefore, we clustered six PEDV haplotypes in China, whereas South Korea held five haplotypes, including a unique haplotype G. In addition, an assessment of the spatiotemporal spread route of PEDV indicates Germany and Japan as the primary hubs for PEDV dissemination in Europe and Asia, respectively. Overall, our findings provide novel insights into the epidemiology, evolution, and transmission of PEDV, and thus may lay a foundation for the prevention and control of PEDV and other coronaviruses.

Association of severity of menstrual dysfunction with cardiometabolic risk markers among women with polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is associated with a wide range of unfavorable cardiometabolic risk factors, including obesity, hypertension, insulin resistance, impaired glucose metabolism, dyslipidemia, and metabolic syndrome. Compared with women with regular menstrual cycles, women with a history of irregular menstrual periods have an increased unfavorable cardiometabolic risk. Recently, the association between the severity of oligomenorrhea and hyperinsulinemia and insulin resistance has been demonstrated. However, evidence linking the severity of menstrual cyclicity with cardiometabolic risk in PCOS women is scarce. MATERIAL AND METHODS: This work was a prospective cross-sectional study. A total of 154 women diagnosed with PCOS by the Rotterdam criteria were recruited from July 2021 to September 2022. PCOS women with eumenorrheic (eumeno group), oligomenorrhea (oligo group), and amenorrhea (ameno group) underwent history and physical examination, gonadal steroid hormone measurement, lipid profile, oral glucose tolerance test, and homeostasis model assessment of insulin resistance. RESULTS: A trend toward an increase in unfavorable cardiometabolic risk markers including obesity, hypertension, prevalence of insulin resistance, prediabetes, dyslipidemia, and metabolic syndrome was observed in the ameno group (n = 57) as compared with the eumeno (n = 24) or oligo group (n = 73). A higher prevalence of insulin resistance (odds ratio [OR]: 3.02; 95% confidence interval [CI]: 1.03-8.81) and prediabetes (OR: 3.94; 95% CI: 1.01-15.40) was observed in the ameno group than in the eumeno group, and a higher proportion of dyslipidemia (OR: 2.44; 95% CI: 1.16-5.15) was observed in the ameno group than in the oligo group in the binary logistic regression analysis after adjusting for confounding factors. CONCLUSIONS: PCOS women with amenorrhea show a higher prevalence of insulin resistance, prediabetes, and dyslipidemia compared with those with oligomenorrhea or eumenorrhea. The severity of menstrual dysfunction could be used as a readily obtainable marker for the identification of PCOS women at greatest risk of cardiometabolic diseases.

Efficacy of three-dimensional arterial spin labeling and how it compares against that of contrast enhanced magnetic resonance imaging in preoperative grading of brain gliomas.

PURPOSE: To evaluate the efficacy of three-dimensional arterial spin labeling (3D-ASL) imaging in preoperative grading of brain gliomas, and compare the discrepancy between images obtained from 3D-ASL and contrast enhanced magnetic resonance imaging (CE-MRI) in grading of gliomas. METHODS: Fifty-one patients with brain gliomas received plain MRI, CE-MRI and 3D-ASL scanning before surgery. In 3D-ASL images, the maximum tumor blood flow (TBF) of tumor parenchyma was measured, relative TBF-M and rTBF-WM were calculated. The cases were categorized into "ASL dominant" and "CE dominant" to compare the discrepancy between 3D-ASL and CE-MRI results. Independent samples t test, Mann-Whitney and U test and one-way analysis of variance (ANOVA) were performed to test the differences of TBF, rTBF-M and rTBF-WM values among brain gliomas with different grades. Spearman rank correlation analysis was performed to assess the correlation between TBF, rTBF-M, rTBF-WM and glioma grades respectively. To compare the discrepancy between 3D-ASL and CE-MRI results. RESULTS: In high-grade gliomas (HGG) group, TBF, rTBF-M and rTBF-WM values were higher than those in low-grade gliomas (LGG) group (p < .05). Multiple comparison showed TBF and rTBF-WM values were different between grade I and IV gliomas, grade II and IV gliomas (both p < .05), the rTBF-M value was different between grade I and IV gliomas (p < .05). The values of all 3D-ASL derived parameters were positively correlated with gliomas grading (all p < .001). TBF showed highest specificity (89.3%) and rTBF-WM showed highest sensitivity (96.4%) when discriminating LGG and HGG using ROC curve. There were 29 CE dominant cases (23 cases were HGG), 9 ASL dominant cases (4 cases were HGG). CONCLUSION: 3D-ASL is of significance to preoperative grading of brain gliomas and might be more sensitive than CE-MRI in detection of tumor perfusion.

12/15-Lipoxygenase Regulation of Diabetic Cognitive Dysfunction Is Determined by Interfering with Inflammation and Cell Apoptosis.

This study aimed to discuss the role of 12/15-lipoxygenase (12/15-LOX) regulation involved in diabetes cognitive dysfunction. First, Mini Mental State Examination (MMSE) test was used to evaluate cognitive ability in diabetic patients and normal controls. The plasma test showed that the plasma level of 12/15-LOX in patients with MMSE scores below 27 was significantly increased compared with that of the normal group. Second, 12/15-LOX inhibitor was administered to diabetic rats. Behavioral tests, biochemistry, enzyme-linked immunosorbent assays, and Western blotting were used in this study. We found that the levels of fasting and random blood glucose increased rapidly in diabetic rats, the levels of triglycerides and total cholesterol in the diabetic group increased, and insulin levels decreased significantly. In the Morris water maze test, the escape latency was prolonged, and the crossing times decreased in the diabetic group. Under the microscope, the apoptosis of hippocampal neurons in diabetic rats increased significantly. The levels of TNF-α, IL-6 and 12-hydroxyindoleic acid (12(S)-HETE) significantly increased, and the protein expression of 12/15-LOX, p38 MAPK, Aß1-42, caspase-3, caspase-9 and cPLA2 increased, while that of Bcl-2 decreased. However, the use of 12/15-LOX inhibitor reversed these results. Third, 12/15-LOX shRNA and p38MAPK inhibitor were administered to HT22 cells in high-glucose medium. The results of the cell experiment were consistent with those of the animal experiment. Our results indicated that the 12/15-LOX pathway participates in diabetic brain damage by activating p38MAPK to promote inflammation and neuronal apoptosis, and intervention 12/15-LOX can improve diabetic cognitive dysfunction.

Evolution Analysis of Free Fatty Acids and Aroma-Active Compounds during Tallow Oxidation.

To explore the role of fatty acids as flavor precursors in the flavor of oxidized tallow, the volatile flavor compounds and free fatty acid (FFAs) in the four oxidization stages of tallow were analyzed via gas chromatography (GC)-mass spectrometry (MS), the aroma characteristics of them were analyzed by GC-olfactory (GC-O) method combined with sensory analysis and partial least-squares regression (PLSR) analysis. 12 common FFAs and 35 key aroma-active compounds were obtained. Combined with the results of odor activity value (OAV) and FD factor, benzaldehyde was found to be an important component in unoxidized tallow. (E,E)-2,4-Heptadienal, (E,E)-2,4-decadienal, (E)-2-nonenal, octanal, hexanoic acid, hexanal and (E)-2-heptenal were the key compounds involved in the tallow flavor oxidation. The changes in FFAs and volatile flavor compounds during oxidation and the metabolic evolution of key aroma-active compounds are systematically summarized in this study. The paper also provides considerable guidance in oxidation control and meat flavor product development.

The induction and characterization of monoclonal antibodies specific to GP of Ebola virus.

The Ebola virus is highly infectious and characterized by hemorrhagic fever, headache, and so on with a high mortality rate. Currently, there are neither therapeutic drugs or vaccines against the Ebola virus nor fast diagnostic methods for the detection of Ebola virus infection. This study reported the induction and isolation of two monoclonal antibodies that specifically recognized the glycoprotein (GP) and secreted glycoprotein (sGP) of the Ebola virus. Plasmids encoding either GP or sGP were constructed and immunized BALB/c mice, accordingly purified sGP was boosted. The antisera were analyzed for binding activity against sGP protein in enzyme-linked immunosorbent assay (ELISA) and neutralization activity in a pseudotyped virus neutralization assay. A number of reactive clones were isolated and two monoclonal antibodies T231 and T242 were identified to react with both GP and sGP. Western blot and ELISA assays showed that the monoclonal antibodies could react with GP and sGP, respectively. Moreover, they could recognize Ebola pseudovirus by cellular immunochemistry assay. We labeled the monoclonal antibody T231 with biotin and analyzed the competitiveness of the two antibodies by the ELISA test. The results showed that the binding epitopes of the two monoclonal antibodies to sGP were partially overlapped. In summary, two GP-specific mAbs were identified, which will be used to detect the Ebola virus or investigate GP.

Greater efficacy of SPF 100+ sunscreen compared with SPF 50+ in sunburn prevention during 5 consecutive days of sunlight exposure: A randomized, double-blind clinical trial.

BACKGROUND: Beach vacations are high-risk settings for overexposure to ultraviolet radiation. OBJECTIVE: To compare the sunburn protective efficacy of SPF 50+ and SPF 100+ sunscreens under actual use at the beach. METHODS: A prospective, randomized, double-blind, single-center, split-body/face study of 55 healthy individuals. Each participant applied both sunscreens to randomized sides of the face/body for up to 5 consecutive days. Blinded clinical evaluation of erythema by a single grader and objective instrumental assessments, colorimetry, and diffuse reflectance spectroscopy were performed the morning after each sun exposure. RESULTS: After 5 days, 31 (56%) participants had more sunburn on the SPF 50+ side compared to 4 (7%) on the SPF 100+ side. Overall, mean erythema intensity showed statistically significantly less erythema on the SPF 100+ side compared with the SPF 50+ side. The first observation of sunburn exclusively on the SPF 50+ side occurred after 1 day of sun exposure, whereas that for SPF 100+ occurred after 3 days of sun exposure. LIMITATIONS: Only initial sunscreen application was monitored, only 1 participant with skin phototype I was recruited, and participants were recruited from a local beach area. CONCLUSION: SPF 100+ was significantly more effective in protecting against ultraviolet radiation-induced erythema and sunburn than SPF 50+ in actual use in a beach vacation setting.

Optical color image encryption based on chaotic fingerprint phase mask in various domains and comparative analysis.

Random phase masks serve as secret keys and play a vital role in double random phase encoding architecture. In this paper, we propose a new, to the best of our knowledge, method to generate the random phase masks using the chaotic Henon map and fingerprint. We then extend the generated chaotic fingerprint phase masks to the Fourier transform domain, fractional Fourier transform domain, Fresnel transform domain, and Gyrator transform domain to encrypt color images. In these four color image encryption schemes, the fingerprint and chaotic parameters serve as secret keys directly, and the chaotic fingerprint phase masks are just used as interim variables and functions. If the sender and receiver share the fingerprint, only the chaotic parameters are needed to transmit over the network. Thus, the management and transmission of the secret keys in these four encryption schemes are convenient. In addition, the fingerprint keys which are strongly linked with the sender or receiver can enhance the security of these four encryption schemes greatly. Extensive numerical simulations have been carried out to verify the feasibility, security, and robustness of these four color image encryption schemes.

Knockdown of long noncoding RNA HOTAIR inhibits cell growth of human lymphoma cells by upregulation of miR-148b.

Lymphoma is a common cause of cancer worldwide with an increasing incidence in recent years. A large number of studies have shown that HOX transcript antisense intergenic RNA (HOTAIR) exerts as an oncogene in various neoplasms. However, the function of HOTAIR in lymphoma still remains unclear. The present study aimed to investigate the function of HOTAIR in lymphoma and its underlying mechanisms. The expressions of HOTAIR, miR-148b, and BMI1 in lymphoma samples and cells (AHH-1, Raji, and U937) were quantified by quantitative reverse polymerase chain reaction (qRT-PCR). Cell viability was measured by trypan blue assay. The efficiency of transfection was verified by qRT-PCR or Western blot analysis. Apoptotic cells and cell cycle progression were both detected by flow cytometry assay. Furthermore, Western blot analysis was performed to assess the expression of mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) pathway-related core factors. We found that HOTAIR knockdown reduced cell viability but increased apoptotic cells and inhibited cell cycle progression in Raji and U937 cells. miR-148b expression was upregulated by HOTAIR inhibition. Meanwhile, miR-148b inhibitor abolished the modulation of HOTAIR silence on cell growth, as evidenced by increased cell viability, reduced apoptotic cells, and decreased the rate of G1 phase cells. Furthermore, miR-148b negatively regulated the expression of BMI1 by targeting its 3'-untranslated region (3'-UTR), and BMI1 overexpression blocked the effect of miR-148b mimic on cell growth. In addition, BMI1 promoted the activation of MAPK and ERK in Raji and U937 cells. In conclusion, the present study demonstrated that HOTAIR knockdown inhibited the cell growth and promoted apoptosis of lymphoma cells via upregulation of miR-148b and miR-148b further regulated the expression of BMI1 via MAPK and ERK signaling pathways.

Double-Edged Effect of Hydroxychloroquine on Human Umbilical Cord-Derived Mesenchymal Stem Cells Treating Lupus Nephritis in MRL/lpr Mice.

Hydroxychloroquine (HCQ) and human umbilical cord-derived mesenchymal stem cells (UC-MSCs) were used to treat systemic lupus erythematosus (SLE), respectively. However, the effect of HCQ on UC-MSCs in lupus nephritis (LN) has not been investigated. In this study, HCQ and UC-MSCs were used in MRL/lpr mice. Surprisingly, although the treatment of both HCQ and UC-MSCs could ameliorate renal damage separately, the presence of HCQ decreased unexpectedly the therapeutic effects of UC-MSCs through interfering expression of IFN-γ. However, HCQ-pretreated UC-MSCs showed significant improvements of renal morphology and function more rapidly than that of UC-MSCs and HCQ alone. To test the role of HCQ in UC-MSCs, MRL/lpr mice and SLE patients' peripheral blood were used in vivo and in vitro. Results showed that after administration of UC-MSCs pretreated by HCQ, CXCR3 expression in renal tissues, serum IL-2, and IgM levels decreased significantly, and serum IL-10 level increased significantly. HCQ pretreatment caused a significant decrease of TNF-α and MCP-1 secretion and an increase of IL-1ß and CXCL10 release from UC-MSCs. Our results indicate that HCQ plays a double-edged role in UC-MSCs. It is necessary for clinical treatment to pre-evaluated concomitant application of UC-MSCs with HCQ. More importantly, the alterative expression of IFN-γ, the improvement of migration ability of UC-MSCs, the regulation of Th1/Th2 balance, and the changes of antibodies secretion in B cell might be involved in its mechanisms.

Interleukin 6 (IL-6) and Tumor Necrosis Factor α (TNF-α) Single Nucleotide Polymorphisms (SNPs), Inflammation and Metabolism in Gestational Diabetes Mellitus in Inner Mongolia.

BACKGROUND Gestational diabetes mellitus (GDM) is common all over the world. GDM women are with inflammatory and metabolisms abnormalities. However, few studies have focused on the association of IL-65-72C/G and TNF-α -857C/T single nucleotide polymorphisms (SNPs), inflammatory biomarkers, and metabolic indexes in women with GDM, especially in the Inner Mongolia population. The aim of this study was to investigate the associations of IL-65-72C/G and TNF-α -857C/T SNPs, and inflammation and metabolic biomarkers in women with GDM pregnancies. MATERIAL AND METHODS Blood samples and placentas from 140 women with GDM and 140 women with healthy pregnancies were collected. Matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) and MassARRAY-IPLEX were performed to analyze IL-65-72C/G and TNF-α -857C/T SNPs. Enzyme linked immunosorbent assay (ELISA) was performed to analyze inflammatory biomarkers and adipokines. RESULTS Distribution frequency of TNF-α -857CT (OR=3.316, 95% CI=1.092-8.304, p=0.025) in women with GDM pregnancies were obviously higher than that in women with healthy pregnancies. Women with GDM were of older maternal age, had higher BMI, were more nulliparous, and had T2DM and GDM history, compared to women with healthy pregnancies (p<0.05). Inflammatory biomarkers in serum (hs-CRP, IL-6, IL-8, IL-6/IL-10 ratio) and placental (NF-κB, IL-6, IL-8, IL-6/IL-10 ratio, IL-1b, TNF-α) were significantly different (p<0.05) between women with GDM and women with healthy pregnancies. Differences were found for serum FBG, FINS, HOMA-IR, and HOMA-ß, and placental IRS-1, IRS-2, leptin, adiponectin, visfatin, RBP-4, chemerin, nesfatin-1, FATP-4, EL, LPL, FABP-1, FABP-3, FABP-4, and FABP-5. CONCLUSIONS TNF-α -857C/T SNP, hs-CRP, IL-6, IL-8, and IL-6/IL-10 were associated with GDM in women from Inner Mongolia, as was serious inflammation and disordered lipid and glucose metabolisms.

5-lipoxygenase activation is involved in the mechanisms of chronic hepatic injury in a rat model of chronic aluminum overload exposure.

We previously confirmed that rats overloaded with aluminum exhibited hepatic function damage and increased susceptibility to hepatic inflammation. However, the mechanism of liver toxicity by chronic aluminum overload is poorly understood. In this study, we investigated changes in the 5-lipoxygenase (5-LO) signaling pathway and its effect on liver injury in aluminum-overloaded rats. A rat hepatic injury model of chronic aluminum injury was established via the intragastric administration of aluminum gluconate (Al(3+) 200mg/kg per day, 5days a week for 20weeks). The 5-LO inhibitor, caffeic acid (10 and 30mg/kg), was intragastrically administered 1h after aluminum administration. Hematoxylin and eosin staining was used to visualize pathological changes in rat liver tissue. A series of biochemical indicators were measured with biochemistry assay or ELISAs. Immunochemistry and RT-PCR methods were used to detect 5-LO protein and mRNA expression in the liver, respectively. Caffeic acid administration protected livers against histopathological injury, decreased plasma ALT, AST, and ALP levels, decreased TNF-α, IL-6, IL-1ß and LTs levels, increased the reactive oxygen species content, and down-regulated the mRNA and protein expressions of 5-LO in aluminum overloaded rats. Our results indicate that 5-lipoxygenase activation is mechanistically involved in chronic hepatic injury in a rat model of chronic aluminum overload exposure and that the 5-LO signaling pathway, which associated with inflammation and oxidative stress, is a potential therapeutic target for chronic non-infection liver diseases.

Effect of Melatonin and Resveratrol against Memory Impairment and Hippocampal Damage in a Rat Model of Vascular Dementia.

OBJECTIVES: This study was intended to investigate whether treatment with resveratrol and melatonin alone or in combination can exert neurorestorative effects in a rat model of vascular dementia. METHODS: Briefly, male Wistar rats were subjected to permanent bilateral common carotid artery occlusion (BCCAO) by surgery. After 4 weeks, the cognitive deficits were assessed using the Morris water maze and novel object recognition tests. The biochemical parameters of oxidative stress and inflammation were also assessed. RESULTS: Rats in the BCCAO group showed cognitive deficits, accompanied by oxidonitrosative stress, neuroinflammation, and a reduction in brain-derived neurotrophic factor (BDNF) in the hippocampus region. Moreover, the acetylcholinesterase activity in the hippocampus was found to be increased in the BCCAO group compared to the sham group. The 4-week treatment with melatonin (10 mg/kg) and resveratrol (20 mg/kg) alone and in combination (melatonin 5 mg/kg and reseveratrol 10 mg/kg) caused a significant improvement in the cognitive deficits induced by BCCAO, accompanied by a reversal of oxidonitrosative stress, neuroinflammation, and BDNF depletion in the hippocampus region. Additionally, the treatment with melatonin and resveratrol significantly decreased acetylcholinesterase activity compared to in the BCCAO group. Melatonin and resveratrol ameliorated the BDNF expression of hippocampal protein. CONCLUSION: These results emphasize that coadministration of melatonin and resveratrol can be beneficial in BCCAO-induced vascular dementia through changes in BDNF expressions.

Short- and long-term efficacy and safety of triple vs. dual antithrombotic therapy in patients with drug-eluting stent implantation and an indication for oral anticoagulation: a meta-analysis.

BACKGROUND: The optimal antithrombotic regimen after coronary stenting in patients taking oral anticoagulants (OACs) is still unclear. Therefore, this meta-analysis focused on the short- and long-term efficacy and safety of triple therapy (TT: OAC, aspirin, and thienopyridine) and dual therapy (DT: OAC plus single antiplatelet drug or aspirin plus thienopyridine). METHODS: We searched PubMed, Embase, the Cochrane Library, Wangfang database, and Google Scholar up to December 1, 2015 (January 1, 2000 - December 2015), from randomized and nonrandomized studies comparing TT and DT in patients with OACs undergoing drug-eluting stent (DES) implantation. Major adverse cardiac and cerebrovascular events (MACCE) were the main outcome. Safety outcome was major bleeding (MB). RESULTS: Of 964 publications identified, 1 randomized study and 27 nonrandomized studies of 31,346 patients were included. Overall, TT and OAC plus clopidogrel were associated with a lower risk of MACCE, stroke, MI, and allcause mortality compared with dual antiplatelet therapy or OAC plus aspirin. Additionally, short-term use of triple antithrombotic regimen with OAC, aspirin, and clopidogrel is associated with equivalent risk of major bleeding and decreased rate of MACCE. Long-term use of OAC plus clopidogrel after TT was associated with equal or better benefit and safety outcomes. CONCLUSION: For patients on OAC after coronary stenting, triple therapy (OAC, aspirin, clopidogrel) should be considered in the short term, followed by more long-term therapy with OAC plus clopidogrel. More randomized studies are needed to confirm these findings.

Transcriptome sequencing and analysis of rubber tree (Hevea brasiliensis Muell.) to discover putative genes associated with tapping panel dryness (TPD).

BACKGROUND: Tapping panel dryness (TPD) involves in the partial or complete cessation of latex flow thus seriously affect latex production in rubber tree (Hevea brasiliensis). Numerous studies have been conducted to define its origin and nature, but the molecular nature and mechanism of TPD occurrence remains unknown. This study is committed to de novo sequencing and comparative analysis of the transcriptomes of healthy (H) and TPD-affected (T) rubber trees to identify the genes and pathways related to the TPD. RESULTS: Total raw reads of 34,632,012 and 35,913,020 bp were obtained from H and T library, respectively using Illumina Hiseq 2000 sequencing technology. De novo assemblies yielded 141,456 and 169,285 contigs, and 96,070 and 112,243 unigenes from H and T library, respectively. Among 73597 genes, 22577 genes were identified as differential expressed genes between H and T library via comparative transcript profiling. A majority of genes involved in natural rubber biosynthesis and jasmonate synthesis with most potential relevance in TPD occurrence were found to be differentially expressed. CONCLUSIONS: In TPD-affected trees, the expression of most genes related to the latex biosynthesis and jasmonate synthesis was severely inhibited and is probably the direct cause of the TPD. These new de novo transcriptome data sets provide a significant resource for the discovery of genes related to TPD and improve our understanding of the occurrence and maintainace of TPD.

Identification and pathogenicity of a variant porcine epidemic diarrhea virus field strain with reduced virulence.

BACKGROUND: Since 2010, a variant Porcine epidemic diarrhea virus (PEDV), which causes an acute, highly contagious, and devastating viral enteric disease with a high mortality rate in suckling pigs, broke out in China and spread rapidly to neighboring countries, even to the North America. This virus gradually became the main subtype of PEDV worldwide. However, there were no reports of mild pathogenicity of a variant porcine epidemic diarrhea virus in China. FINDINGS: In 2013, a PEDV-positive sample from a sow with very mild clinical sign was used to inoculate in Vero cells to isolate the virus. This PEDV field strain, designated FL2013 strain, was successfully propagated and genetically characterized. The phylogenetic trees based upon either the complete genome or S gene showed that the FL2013 strain belongs to the genogroup G2b. The S gene of FL2013 has a 7-aa deletion (FEKVHVQ) in the C-terminus comparison with the other G2 PEDV sequences. Further comparative pathology study indicated that the FL2013 strain had reduced virulence to newborn piglets. CONCLUSIONS: A novel variant PEDV strain FL2013 with reduced virulence, as determined by the pathological study, was identified from east China. This strain is closely related to the genogroup-2 PEDV strains prevalent in the U.S. and China currently, but had a short deletion at the 3'-end of the spike gene.

A novel linear B cell epitope of the canine coronavirus nucleocapsid protein identified by a monoclonal antibody.

The infection of canine coronavirus (CCoV) causes a highly contagious disease in dogs with acute gastroenteritis. The efficient serological diagnostics is critical for controlling the disease caused by CCoV. Nucleocapsid (N) protein of CCoV is an important target for developing serological approaches. However, little is known about the antigenic sites in the N protein of CCoV. In this study, we generated a monoclonal antibody (mAb) against the N protein of CCoV, designated as 13E8, through the fusion of the sp2/0 cells with the spleen cells from a mouse immunized with the purified recombinant GST-N protein. Epitope mapping revealed that mAb 13E8 recognized a novel linear B cell epitope in N protein at 294-314aa (named as EP-13E8) by using a serial of truncated N protein through Western blot and ELISA. Sequence analysis showed that the sequence of EP-13E8 was highly conserved (100 %) among different CCoV strains analyzed, but exhibited a low similarity (31.8-63.6 %) with the responding sequence in other coronaviruses of the same genus such as FCoV, PEDV and HCoV except for TGEV (95.5 % identity). Structural assay suggested that the epitope of EP-13E8 were located in the close proximity on the surface of the N protein. Overall, the mAb 13E8 against N protein generated and its epitope EP-13E8 identified here paid the way for further developing epitope-based serological diagnostics for CCoV.

Case report: Shingles-associated probable Bickerstaff brainstem encephalitis with IgM anti-sulfatide positivity.

Background: Bickerstaff brainstem encephalitis (BBE) is a rare disease considered caused by acute demyelination of the brainstem, most often resulting from secondary autoimmune responses. To our knowledge, this is the first probable case report of shingles-associated BBE with anti-sulfatide IgM positivity. Case presentation: We report the case of an 83-year-old woman with symptoms of progressive limb weakness, difficulty swallowing food, and disturbed consciousness that occurred 4 weeks following herpes zoster infection. Autoimmune anti-sulfatide antibodies were positive and fluid-attenuated inversion recovery (FLAIR) sequences revealed clear high signal intensity in pons and bilateral thalamus. Our patient's condition improved markedly with glucocorticoid treatment. After 2 months of treatment, our patient was fully recovered. We considered that for her case, BBE is the most appropriate diagnosis. Conclusions: We emphasize the importance of a careful medical history and assessment of clinical symptoms, performing MRI, testing autoimmune antibodies for rapid diagnosis, and ruling out differential diagnoses. Further studies involving more patients with BBE with IgM anti-sulfatide autoantibodies will increase the understanding of the clinical characteristics and advance the diagnosis and treatment of this syndrome. Meanwhile, it is crucial for dermatologists to know about this severe neurological complication following shingles.

Pan-genome insights into adaptive evolution of bacterial symbionts in mixed host-microbe symbioses represented by human gut microbiota Bacteroides cellulosilyticus.

Animal hosts harbor diverse assemblages of microbial symbionts that play crucial roles in the host's lifestyle. The link between microbial symbiosis and host development remains poorly understood. In particular, little is known about the adaptive evolution of gut bacteria in host-microbe symbioses. Recently, symbiotic relationships have been categorized as open, closed, or mixed, reflecting their modes of inter-host transmission and resulting in distinct genomic features. Members of the genus Bacteroides are the most abundant human gut microbiota and possess both probiotic and pathogenic potential, providing an excellent model for studying pan-genome evolution in symbiotic systems. Here, we determined the complete genome of an novel clinical strain PL2022, which was isolated from a blood sample and performed pan-genome analyses on a representative set of Bacteroides cellulosilyticus strains to quantify the influence of the symbiotic relationship on the evolutionary dynamics. B. cellulosilyticus exhibited correlated genomic features with both open and closed symbioses, suggesting a mixed symbiosis. An open pan-genome is characterized by abundant accessory gene families, potential horizontal gene transfer (HGT), and diverse mobile genetic elements (MGEs), indicating an innovative gene pool, mainly associated with genomic islands and plasmids. However, massive parallel gene loss, weak purifying selection, and accumulation of positively selected mutations were the main drivers of genome reduction in B. cellulosilyticus. Metagenomic read recruitment analyses showed that B. cellulosilyticus members are globally distributed and active in human gut habitats, in line with predominant vertical transmission in the human gut. However, existence and/or high abundance were also detected in non-intestinal tissues, other animal hosts, and non-host environments, indicating occasional horizontal transmission to new niches, thereby creating arenas for the acquisition of novel genes. This case study of adaptive evolution under a mixed host-microbe symbiosis advances our understanding of symbiotic pan-genome evolution. Our results highlight the complexity of genetic evolution in this unusual intestinal symbiont.

LCN2: Versatile players in breast cancer.

Lipocalin 2 (LCN2) is a secreted glycoprotein that is produced by immune cells, including neutrophils and macrophages. It serves various functions such as transporting hydrophobic ligands across the cellular membrane, regulating immune responses, keeping iron balance, and fostering epithelial cell differentiation. LCN2 plays a crucial role in several physiological processes. LCN2 expression is upregulated in a variety of human diseases and cancers. High levels of LCN2 are specifically linked to breast cancer (BC) cell proliferation, apoptosis, invasion, migration, angiogenesis, immune regulation, chemotherapy resistance, and prognosis. As a result, LCN2 has gained attention as a potential therapeutic target for BC. This article offered an in-depth review of the advancement of LCN2 in the context of BC occurrence and development.