Potential pandemic risk of circulating swine H1N2 influenza viruses.

Influenza A viruses in swine have considerable genetic diversity and continue to pose a pandemic threat to humans due to a potential lack of population level immunity. Here we describe a pipeline to characterize and triage influenza viruses for their pandemic risk and examine the pandemic potential of two widespread swine origin viruses. Our analysis reveals that a panel of human sera collected from healthy adults in 2020 has no cross-reactive neutralizing antibodies against a α-H1 clade strain (α-swH1N2) but do against a γ-H1 clade strain. The α-swH1N2 virus replicates efficiently in human airway cultures and exhibits phenotypic signatures similar to the human H1N1 pandemic strain from 2009 (H1N1pdm09). Furthermore, α-swH1N2 is capable of efficient airborne transmission to both naïve ferrets and ferrets with prior seasonal influenza immunity. Ferrets with H1N1pdm09 pre-existing immunity show reduced α-swH1N2 viral shedding and less severe disease signs. Despite this, H1N1pdm09-immune ferrets that became infected via the air can still onward transmit α-swH1N2 with an efficiency of 50%. These results indicate that this α-swH1N2 strain has a higher pandemic potential, but a moderate level of impact since there is reduced replication fitness and pathology in animals with prior immunity.

Emergence and ongoing outbreak of ST80 vancomycin-resistant Enterococcus faecium in Guangdong province, China from 2021 to 2023: a multicenter, time-series and genomic epidemiological study.

BACKGROUND: Surveillance systems revealed that the prevalence of vancomycin-resistant Enterococcus faecium (VREfm) has increased. We aim to investigate the epidemiological and genomic characteristics of VREfm in China. METHODS: We collected 20,747 non-redundant E. faecium isolates from inpatients across 19 hospitals in six provinces between January 2018 and June 2023. VREfm was confirmed by antimicrobial susceptibility testing. The prevalence was analyzed using changepoint package in R. Genomic characteristics were explored by whole-genome sequencing. RESULTS: 5.59% (1159/20,747) of E. faecium isolates were resistant to vancomycin. The prevalence of VREfm increased in Guangdong province from 5% before 2021 to 20-50% in 2023 (p < 0.0001), but not in the other five provinces. Two predominant clones before 2021, ST17 and ST78, were substituted by an emerging clone, ST80, from 2021 to 2023 (88.63%, 195/220). All ST80 VREfm from Guangdong formed a single lineage (SC11) and were genetically distant from the ST80 VREfm from other countries, suggesting a regional outbreak. All ST80 VREfm in SC11 carried a new type of plasmid harbouring a vanA cassette, which was embedded in a Tn1546-like structure flanked by IS1678 and ISL3. However, no conjugation-related gene was detected and no transconjugant was obtained in conjugation experiment, indicating that the outbreak of ST80 VREfm could be attributed to clonal transmission. CONCLUSIONS: We revealed an ongoing outbreak of ST80 VREfm with a new vanA-harbouring plasmid in Guangdong, China. This clone has also been identified in other provinces and countries, foreboding a risk of wider spreading shortly. Continuous surveillance is needed to inform public health interventions.

Limiting viral replication in hepatocytes alters Rift Valley fever virus disease manifestations.

Rift Valley fever virus (RVFV) causes mild to severe disease in humans and livestock. Outbreaks of RVFV have been reported throughout Africa and have spread outside Africa since 2000, calling for urgent worldwide attention to this emerging virus. RVFV directly infects the liver, and elevated transaminases are a hallmark of severe RVFV infection. However, the specific contribution of viral replication in hepatocytes to pathogenesis of RVFV remains undefined. To address this, we generated a recombinant miRNA-targeted virus, RVFVmiR-122, to limit hepatocellular replication. MicroRNAs are evolutionarily conserved non-coding RNAs that regulate mRNA expression by targeting them for degradation. RVFVmiR-122 includes an insertion of four target sequences of the liver-specific miR-122. In contrast to control RVFVmiR-184, which contains four target sequences of mosquito-specific miR-184, RVFVmiR-122 has restricted replication in vitro in primary mouse hepatocytes. RVFVmiR-122-infected C57BL/6 mice survived acute hepatitis and instead developed late-onset encephalitis. This difference in clinical outcome was eliminated in Mir-122 KO mice, confirming the specificity of the finding. Interestingly, C57BL/6 mice infected with higher doses of RVFVmiR-122 had a higher survival rate which was correlated with faster clearance of virus from the liver, suggesting a role for activation of host immunity in the phenotype. Together, our data demonstrate that miR-122 can specifically restrict the replication of RVFVmiR-122 in liver tissue both in vitro and in vivo, and this restriction alters the clinical course of disease following RVFVmiR-122 infection. IMPORTANCE Rift Valley fever virus (RVFV) is a hemorrhagic fever virus that causes outbreaks in humans and livestock throughout Africa and has spread to continents outside Africa since 2000. However, no commercial vaccine or treatment is currently available for human use against RVFV. Although the liver has been demonstrated as a key target of RVFV, the contribution of viral replication in hepatocytes to overall RVFV pathogenesis is less well defined. In this study we addressed this question by using a recombinant miRNA-targeted virus with restricted replication in hepatocytes. We gained a better understanding of how this individual cell type contributes to the development of disease caused by RVFV. Techniques used in this study provide an innovative tool to the RVFV field that could be applied to study the consequences of limited RVFV replication in other target cells.

Research progress on pathogenic and therapeutic mechanisms of Enterovirus A71.

In recent years, enterovirus A71 (EV-A71) infection has become a major global public health problem, especially for infants and young children. The results of epidemiological research show that EV-A71 infection can cause acute hand, foot, and mouth disease (HFMD) and complications of the nervous system in severe cases, including aseptic pediatric meningoencephalitis, acute flaccid paralysis, and even death. Many studies have demonstrated that EV-A71 infection may trigger a variety of intercellular and intracellular signaling pathways, which are interconnected to form a network that leads to the innate immune response, immune escape, inflammation, and apoptosis in the host. This article aims to provide an overview of the possible mechanisms underlying infection, signaling pathway activation, the immune response, immune evasion, apoptosis, and the inflammatory response caused by EV-A71 infection and an overview of potential therapeutic strategies against EV-A71 infection to better understand the pathogenesis of EV-A71 and to aid in the development of antiviral drugs and vaccines.

Impact of maternal SARS-CoV-2 booster vaccination on blood and breastmilk antibodies.

Maternal COVID-19 vaccination could protect infants who are ineligible for vaccine through antibody transfer during pregnancy and lactation. We measured the quantity and durability of SARS-CoV-2 antibodies in human milk and infant blood before and after maternal booster vaccination. Prospective cohort of lactating women immunized with primary and booster COVID-19 vaccines during pregnancy or lactation and their infants. Milk and blood samples from October 2021 to April 2022 were included. Anti-nucleoprotein (NP) and anti-receptor binding domain (RBD) IgG and IgA in maternal milk and maternal and infant blood were measured and compared longitudinally after maternal booster vaccine. Forty-five lactating women and their infants provided samples. 58% of women were anti-NP negative and 42% were positive on their first blood sample prior to booster vaccine. Anti-RBD IgG and IgA in milk remained significantly increased through 120-170 days after booster vaccine and did not differ by maternal NP status. Anti-RBD IgG and IgA did not increase in infant blood after maternal booster. Of infants born to women vaccinated in pregnancy, 74% still had positive serum anti-RBD IgG measured on average 5 months after delivery. Infant to maternal IgG ratio was highest for infants exposed to maternal primary vaccine during the second trimester compared to third trimester (0.85 versus 0.29; p<0.001). Maternal COVID-19 primary and booster vaccine resulted in robust and long-lasting transplacental and milk antibodies. These antibodies may provide important protection against SARS-CoV-2 during the first six months of life.

Low nitrogen stress-induced transcriptome changes revealed the molecular response and tolerance characteristics in maintaining the C/N balance of sugar beet (Beta vulgaris L.).

Nitrogen (N) is an essential macronutrient for plants, acting as a common limiting factor for crop yield. The application of nitrogen fertilizer is related to the sustainable development of both crops and the environment. To further explore the molecular response of sugar beet under low nitrogen (LN) supply, transcriptome analysis was performed on the LN-tolerant germplasm '780016B/12 superior'. In total, 580 differentially expressed genes (DEGs) were identified in leaves, and 1,075 DEGs were identified in roots (log2 |FC| ≥ 1; q value < 0.05). Gene Ontology (GO), protein-protein interaction (PPI), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses clarified the role and relationship of DEGs under LN stress. Most of the downregulated DEGs were closely related to "photosynthesis" and the metabolism of "photosynthesis-antenna proteins", "carbon", "nitrogen", and "glutathione", while the upregulated DEGs were involved in flavonoid and phenylalanine biosynthesis. For example, GLUDB (glutamate dehydrogenase B) was identified as a key downregulated gene, linking carbon, nitrogen, and glutamate metabolism. Thus, low nitrogen-tolerant sugar beet reduced energy expenditure mainly by reducing the synthesis of energy-consuming amino acids, which in turn improved tolerance to low nitrogen stress. The glutathione metabolism biosynthesis pathway was promoted to quench reactive oxygen species (ROS) and protect cells from oxidative damage. The expression levels of nitrogen assimilation and amino acid transport genes, such as NRT2.5 (high-affinity nitrate transporter), NR (nitrate reductase [NADH]), NIR (ferredoxin-nitrite reductase), GS (glutamine synthetase leaf isozyme), GLUDB, GST (glutathione transferase) and GGT3 (glutathione hydrolase 3) at low nitrogen levels play a decisive role in nitrogen utilization and may affect the conversion of the carbon skeleton. DFRA (dihydroflavonol 4-reductase) in roots was negatively correlated with NIR in leaves (coefficient = -0.98, p < 0.05), suggesting that there may be corresponding remote regulation between "flavonoid biosynthesis" and "nitrogen metabolism" in roots and leaves. FBP (fructose 1,6-bisphosphatase) and PGK (phosphoglycerate kinase) were significantly positively correlated (p < 0.001) with Ci (intercellular CO2 concentration). The reliability and reproducibility of the RNA-seq data were further confirmed by real-time fluorescence quantitative PCR (qRT-PCR) validation of 22 genes (R2 = 0.98). This study reveals possible pivotal genes and metabolic pathways for sugar beet adaptation to nitrogen-deficient environments.

Tolerance and adaptation characteristics of sugar beet (Beta vulgaris L.) to low nitrogen supply.

Nitrogen (N) is an essential element required for sugar beet growth. Sugar beets with low N (LN) tolerance and high N use efficiency are excellent materials for breeding. Here, we comprehensively evaluated the morphological and physiological responses of nine sugar beet genotypes to LN supply. It was found that 0.5 mmol·L-1 N (LN) significantly influenced the performance of leaves and the topology of roots by reducing the bioproduction of chlorophyll a (Chl a) and soluble protein (SP) and the accumulation of N in leaves and roots (LNA and RNA), thus differentially restricting the growth (hypocotyl diameter, HD; root length, RL) and biomass (leaf and root fresh weight; LFW and RFW; leaf dry weight, LDW) of these sugar beets. Principal component and cluster analyses showed that 780016B/12 superior (F) exhibited excellent tolerance to LN; it had higher SOD activity (62.70%) and APX activity (188.92%) and a higher proline content (131.82%) than 92011 (G, LN sensitive). These attributes helped 780016B/12 superior (F) to better endure LN stress, and the morphology and N distribution changed to adapt to N deficiency, such that the root length increased by 112.48%, leaf area increased by 101.23%, and leaf nitrogen accumulation reached a peak of 14.13 g/plant. It seems that LN-tolerant genotypes increased their root length and surface area by reducing the difference in biomass, thereby expanding the contact between roots and soil, which was conducive to the absorption of nutrients (N) by sugar beets and helped distribute more assimilation products to the roots.

Multi­locus sequence and drug resistance analysis of Salmonella infection in children with diarrhea in Guangdong to identify the dominant ST and cause of antibiotic­resistance.

Multi-locus sequence typing (MLST) can be used to analyze the homology among the drug resistance gene cassettes in Salmonella and determine the prevalence. Information extracted using this technique can provide a theoretical basis for hospitals to devise protocols to control Salmonella infections. The aim of the present study was to investigate the possible association between drug resistance and integrons in clinical isolates of Salmonella from human fecal samples. Therefore, in the present study, 52 clinical fecal isolates of non-duplicate (i.e., not genome contamination) Salmonella were harvested from children with diarrhea and used for bacterial identification using biochemical tests, drug susceptibility analysis by antibiotic susceptibility testing and serotype identification using an agglutination assay. In total, seven Salmonella housekeeping genes (chorismate synthase, ß sliding clamp of DNA polymerase III, uroporphyrinogen-III synthase, histidinol dehydrogenase, phosphoribosylaminoimidazole carboxylase catalytic subunit, 2-oxoglutarate dehydrogenase E1 component and homoserine dehydrogenase) were amplified and sequenced using MLST, before sequence alignment was performed against the Pub MLST database to determine the sequence-typed (ST) strains and construct genotypic evolutionary diagrams. Subsequently, the 52 Salmonella strains were subdivided into 11 serotypes and 11 sequence types. The dominant subtypes were found to be Salmonella typhimurium ST34 and ST19, which were diversely distributed. However, no new subtypes were found. Although the serotypes, including ST19, ST29, ST34, ST40, ST11, ST27, ST469, ST365, ST1499, ST413 and ST588, were closely associated with the MLST subtype, they did not correspond entirely. The detection rate of class I integrons was 38.46% (20/52), but no class II and III integrons were detected. The variable regions of three of 20 class I integrons were found to be amplified, whereas nine gene cassettes, including dihydrofolate reductase A12, open reading frame F, aminoglycoside-adenylyltransferase (aad)A2, aadA22, aadA23, aadA1, cadmium-translocating P-type ATPase 2, lincosamide and linF, were associated with drug resistance. These data suggest that Class I integrons are important factors underlying drug resistance in Salmonella, which may serve a role in the spread of drug resistance and warrant specific focus. In addition, MLST typing and serotyping should be applied cooperatively in epidemiological research.

Acclimation of sugar beet in morphological, physiological and BvAMT1.2 expression under low and high nitrogen supply.

Understanding the response and tolerance mechanisms of nitrogen (N) stress is essential for the taproot plant of sugar beet. Hence, in this study, low (0.5 and 3 mmol/L; N0.5 and N3), moderate (5 mmol/L; N5; control) and high (10 and 12 mmol/L; N10 and N12) N were imposed to sugar beet to comparatively investigate the growth and physiological changes, and expression pattern of the gene involving ammonia transporting at different seedling stages. The results showed that, different from N5 which could induce maximum biomass of beet seedlings, low N was more likely to inhibit the growth of beet seedlings than high N treatments. Morphological differences and adverse factors increased significantly with extension of stress time, but sugar beet seedlings displayed a variety of physical responses to different N concentrations to adapt to N abnormal. At 14 d, the chlorophyll content, leaf and root surface area, total dry weight and nitrogen content of seedlings treated with N0.5 decreased 15.83%, 53.65%, 73.94%, 78.08% and 24.88% respectively, compared with N12; however, the root shoot ratio increased significantly as well as superoxide dismutase (SOD), peroxidase (POD), glutamine synthetase (GS) activity and malondialdehyde (MDA) and proline content, especially in root. The expression of BvAMT1.2 was also regulated in an N concentration-dependent manner, and was mainly involved in the tolerance of beet leaves to N stress, which significantly positively correlated to GS activity on the basis of its high affinity to N. It can be deduced that the stored nutrients under low N could only maintain relatively stable root growth, and faced difficulty in being transported to the shoots. Sugar beet was relatively resilient to N0.5 stress according to the mean affiliation function analysis. These results provide a theoretical basis for the extensive cultivation of sugar beet in N-stressed soil.

Pulmonary Infection Caused by Strongyloides stercoralis.

PURPOSE: Strongyloidiasis is mainly prevalent in developing countries with poor economic and sanitary conditions. The clinical manifestations of Strongyloides stercoralis infection are complex and diverse, lacking specificity, which can easily lead to misdiagnosis and delayed treatment. METHODS: An elderly male patient, repeated cough and expectoration for 4 years, with exacerbation and dyspnea for 10 days, was admitted to hospital. Sputum culture and smear were taken for examination. Nematode larvae were found under the microscope. Nematodes were also found in feces. RESULTS: Upon confirmation, the patient was diagnosed with a pulmonary infection caused by Strongyloides stercoralis. After treatment with albendazole, the symptoms improved, and the patient was discharged. CONCLUSION: In this case report, combination of microscopic examination of sputum and alveolar lavage fluid and CT scan were used to quickly identify the cause of the patient, it provides a diagnostic basis and method for clinical treatment.

Carriage of distinct blaKPC-2 and blaOXA-48 plasmids in a single ST11 hypervirulent Klebsiella pneumoniae isolate in Egypt.

BACKGROUND: Carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) causes serious infections with significant morbidity and mortality. However, the epidemiology and transmission mechanisms of CR-hvKP and the corresponding carbapenem-resistant plasmids require further investigation. Herein, we have characterized an ST11 K. pneumoniae strain EBSI041 from the blood sample encoding both hypervirulence and carbapenem resistance phenotypes from a patient in Egypt. RESULTS: K. pneumoniae strain EBSI041 showed multidrug-resistance phenotypes, where it was highly resistant to almost all tested antibiotics including carbapenems. And hypervirulence phenotypes of EBSI041 was confirmed by the model of Galleria mellonella infection. Whole-genome sequencing analysis showed that the hybrid plasmid pEBSI041-1 carried a set of virulence factors rmpA, rmpA2, iucABCD and iutA, and six resistance genes aph(3')-VI, armA, msr(E), mph(E), qnrS, and sul2. Besides, blaOXA-48 and blaSHV-12 were harboured in a novel conjugative IncL-type plasmid pEBSI041-2. The blaKPC-2-carrying plasmid pEBSI041-3, a non-conjugative plasmid lacking the conjugative transfer genes, could be transferred with the help of pEBSI041-2, and the two plasmids could fuse into a new plasmid during co-transfer. Moreover, the emergence of the p16HN-263_KPC-like plasmids is likely due to the integration of pEBSI041-3 and pEBSI041-4 via IS26-mediated rearrangement. CONCLUSION: To the best of our knowledge, this is the first report on the complete genome sequence of KPC-2- and OXA-48-coproducing hypervirulent K. pneumoniae from Egypt. These results give new insights into the adaptation and evolution of K. pneumoniae during nosocomial infections.

Diagnostic Model for Discrimination Between Tuberculous Meningitis and Bacterial Meningitis.

Background: The differential diagnosis between tuberculous meningitis (TBM) and bacterial meningitis (BM) remains challenging in clinical practice. This study aimed to establish a diagnostic model that could accurately distinguish TBM from BM. Methods: Patients with TBM or BM were recruited between January 2017 and January 2021 at Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort). The detection for indicators involved in cerebrospinal fluid (CSF) and T-SPOT assay were performed simultaneously. Multivariate logistic regression was used to create a diagnostic model. Results: A total of 174 patients (76 TBM and 98 BM) and another 105 cases (39 TBM and 66 BM) were enrolled from Qiaokou cohort and Caidian cohort, respectively. Significantly higher level of CSF lymphocyte proportion while significantly lower levels of CSF chlorine, nucleated cell count, and neutrophil proportion were observed in TBM group when comparing with those in BM group. However, receiver operating characteristic (ROC) curve analysis showed that the areas under the ROC curve (AUCs) produced by these indicators were all under 0.8. Meanwhile, tuberculosis-specific antigen/phytohemagglutinin (TBAg/PHA) ratio yielded an AUC of 0.889 (95% CI, 0.840-0.938) in distinguishing TBM from BM, with a sensitivity of 68.42% (95% CI, 57.30%-77.77%) and a specificity of 92.86% (95% CI, 85.98%-96.50%) when a cutoff value of 0.163 was used. Consequently, we successfully established a diagnostic model based on the combination of TBAg/PHA ratio, CSF chlorine, CSF nucleated cell count, and CSF lymphocyte proportion for discrimination between TBM and BM. The established model showed good performance in differentiating TBM from BM (AUC: 0.949; 95% CI, 0.921-0.978), with 81.58% (95% CI, 71.42%-88.70%) sensitivity and 91.84% (95% CI, 84.71%-95.81%) specificity. The performance of the diagnostic model obtained in Qiaokou cohort was further validated in Caidian cohort. The diagnostic model in Caidian cohort produced an AUC of 0.923 (95% CI, 0.867-0.980) with 79.49% (95% CI, 64.47%-89.22%) sensitivity and 90.91% (95% CI, 81.55%-95.77%) specificity. Conclusions: The diagnostic model established based on the combination of four indicators had excellent utility in the discrimination between TBM and BM.

The Involvement of Mycobacterium Type III-A CRISPR-Cas System in Oxidative Stress.

Type I and type II CRISPR-Cas systems are employed to evade host immunity by targeting interference of bacteria's own genes. Although Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, possesses integrated type III-A CRISPR-Cas system, its role in mycobacteria remains obscure. Here, we observed that seven cas genes (csm2∼5, cas10, cas6) were upregulated in Mycobacterium bovis BCG under oxidative stress treatment, indicating the role of type III-A CRISPR-Cas system in oxidative stress. To explore the functional role of type III-A CRISPR-Cas system, TCC (Type III-A CRISPR-Cas system, including cas6, cas10, and csm2-6) mutant was generated. Deletion of TCC results in increased sensitivity in response to hydrogen peroxide and reduced cell envelope integrity. Analysis of RNA-seq dataset revealed that TCC impacted on the oxidation-reduction process and the composition of cell wall which is essential for mycobacterial envelop integrity. Moreover, disrupting TCC led to poor intracellular survival in vivo and in vitro. Finally, we showed for the first time that TCC contributed to the regulation of regulatory T cell population, supporting a role of TCC in modulating host immunity. Our finding reveals the important role of TCC in cell envelop homeostasis. Our work also highlights type III-A CRISPR-Cas system as an important factor for intracellular survival and host immunoregulation in mycobacteria, thus may be a potential target for therapy.

Multiplex assessment of SARS-CoV-2 antibodies improves assay sensitivity and correlation with neutralizing antibodies.

OBJECTIVES: Detection of antibodies to multiple SARS-CoV-2 antigens in a single assay could increase diagnostic accuracy, differentiate vaccination from natural disease, and aid in retrospective exposure determination. Correlation of binding antibody assessment in clinical assays with neutralizing antibodies is needed to better understand the humoral response to SARS-CoV-2 infection and establish of correlates of protection. METHODS: A cohort of 752 samples was used to assess specificity, sensitivity, and comparison to 6 other Conformitè Europëenne serologic assays for the BioRad SARS-CoV-2 IgG multiplex assay which measures receptor binding domain IgG (RBD), spike-S1 IgG (S1), spike-S2 IgG (S2), and nucleocapsid IgG (N). A subset of serial specimens from 14 patients was also tested for neutralizing antibodies (n = 61). RESULTS: Specificity for RBD and S1 IgG was 99.4% (n = 170) and 100% for S2 and N IgG (n = 170) in a cohort selected for probable interference. Overall assay concordance with other assays was >93% for IgG and total antibody assays and reached 100% sensitivity for clinical concordance at >14 days as a multiplex assay. RBD and S1 binding antibody positivity demonstrated 79-95% agreement with the presence of neutralizing antibodies. CONCLUSIONS: The BioRad SARS-CoV-2 IgG assay is comparable to existing assays, and achieved 100% sensitivity when all markers were included. The ability to measure antibodies against spike and nucleocapsid proteins simultaneously may be advantageous for complex clinical presentations, epidemiologic research, and in decisions regarding infection prevention strategies. Additional independent validations are needed to further determine binding antibody and neutralizing antibody correlations.

Targeting epigenetics and lncRNAs in liver disease: From mechanisms to therapeutics.

Early onset and progression of liver diseases can be driven by aberrant transcriptional regulation. Different transcriptional regulation processes, such as RNA/DNA methylation, histone modification, and ncRNA-mediated targeting, can regulate biological processes in healthy cells, as well also under various pathological conditions, especially liver disease. Numerous studies over the past decades have demonstrated that liver disease has a strong epigenetic component. Therefore, the epigenetic basis of liver disease has challenged our knowledge of epigenetics, and epigenetics field has undergone an important transformation: from a biological phenomenon to an emerging focus of disease research. Furthermore, inhibitors of different epigenetic regulators, such as m6A-related factors, are being explored as potential candidates for preventing and treating liver diseases. In the present review, we summarize and discuss the current knowledge of five distinct but interconnected and interdependent epigenetic processes in the context of hepatic diseases: RNA methylation, DNA methylation, histone methylation, miRNAs, and lncRNAs. Finally, we discuss the potential therapeutic implications and future challenges and ongoing research in the field. Our review also provides a perspective for identifying therapeutic targets and new hepatic biomarkers of liver disease, bringing precision research and disease therapy to the modern era of epigenetics.

A Cross-Sectional Study of SARS-CoV-2 Seroprevalence between Fall 2020 and February 2021 in Allegheny County, Western Pennsylvania, USA.

Seroprevalence studies are important for understanding the dynamics of local virus transmission and evaluating community immunity. To assess the seroprevalence for SARS-CoV-2 in Allegheny County, an urban/suburban county in Western PA, 393 human blood samples collected in Fall 2020 and February 2021 were examined for spike protein receptor-binding domain (RBD) and nucleocapsid protein (N) antibodies. All RBD-positive samples were evaluated for virus-specific neutralization activity. Our results showed a seroprevalence of 5.5% by RBD ELISA, 4.5% by N ELISA, and 2.5% for both in Fall 2020, which increased to 24.7% by RBD ELISA, 14.9% by N ELISA, and 12.9% for both in February 2021. Neutralization titer was significantly correlated with RBD titer but not with N titer. Using these two assays, we were able to distinguish infected from vaccinated individuals. In the February cohort, higher median income and white race were associated with serological findings consistent with vaccination. This study demonstrates a 4.5-fold increase in SARS-CoV-2 seroprevalence from Fall 2020 to February 2021 in Allegheny County, PA, due to increased incidence of both natural disease and vaccination. Future seroprevalence studies will need to include the effect of vaccination on assay results and incorporate non-vaccine antigens in serological assessments.

Emergence of Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae Coharboring a blaNDM-1-Carrying Virulent Plasmid and a blaKPC-2-Carrying Plasmid in an Egyptian Hospital.

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates in Egyptian hospitals has been reported. However, the genetic basis and analysis of the plasmids associated with carbapenem-resistant hypervirulent K. pneumoniae (CR-HvKP) in Egypt have not been presented. Therefore, we attempted to decipher the plasmid sequences that are responsible for transferring the determinants of carbapenem resistance, particularly blaNDM-1 and blaKPC-2 Out of 34 K. pneumoniae isolates collected from two tertiary hospitals in Egypt, 31 were CRKP. Whole-genome sequencing revealed that our isolates were related to 13 different sequence types (STs). The most prevalent ST was ST101, followed by ST383 and ST11. Among the CRKP isolates, one isolate named EBSI036 has been reassessed by Nanopore sequencing. Genetic environment analysis showed that EBSI036 carried 20 antibiotic resistance genes and was identified as a CR-HvKP strain: it harbored four plasmids, namely, pEBSI036-1-NDM-VIR, pEBSI036-2-KPC, pEBSI036-3, and pEBSI036-4. The two carbapenemase genes blaNDM-1 and blaKPC-2 were located on plasmids pEBSI036-1-NDM-VIR and pEBSI036-2-KPC, respectively. The IncFIB:IncHI1B hybrid plasmid pEBSI036-1-NDM-VIR also carried some virulence factors, including the regulator of the mucoid phenotype (rmpA), the regulator of mucoid phenotype 2 (rmpA2), and aerobactin (iucABCD and iutA). Thus, we set out in this study to analyze in depth the genetic basis of the pEBSI036-1-NDM-VIR and pEBSI036-2-KPC plasmids. We report a high-risk clone ST11 KL47 serotype of a CR-HvKP strain isolated from the blood of a 60-year-old hospitalized female patient from the intensive care unit (ICU) in a tertiary care hospital in Egypt, which showed the cohabitation of a novel hybrid plasmid coharboring the blaNDM-1 and virulence genes and a blaKPC-2-carrying plasmid.IMPORTANCE CRKP has been registered in the critical priority tier by the World Health Organization and has become a significant menace to public health. The emergence of CR-HvKP is of great concern in terms of both disease and treatment. In-depth analysis of the carbapenemase-encoding and virulence plasmids may provide insight into ongoing recombination and evolution of virulence and multidrug resistance in K. pneumoniae Thus, this study serves to alert contagious disease clinicians to the presence of hypervirulence in CRKP isolates in Egyptian hospitals.

Glycyrrhizic Acid Nanoparticles as Antiviral and Anti-inflammatory Agents for COVID-19 Treatment.

COVID-19 has been diffusely pandemic around the world, characterized by massive morbidity and mortality. One of the remarkable threats associated with mortality may be the uncontrolled inflammatory processes, which were induced by SARS-CoV-2 in infected patients. As there are no specific drugs, exploiting safe and effective treatment strategies is an instant requirement to dwindle viral damage and relieve extreme inflammation simultaneously. Here, highly biocompatible glycyrrhizic acid (GA) nanoparticles (GANPs) were synthesized based on GA. In vitro investigations revealed that GANPs inhibit the proliferation of the murine coronavirus MHV-A59 and reduce proinflammatory cytokine production caused by MHV-A59 or the N protein of SARS-CoV-2. In an MHV-A59-induced surrogate mouse model of COVID-19, GANPs specifically target areas with severe inflammation, such as the lungs, which appeared to improve the accumulation of GANPs and enhance the effectiveness of the treatment. Further, GANPs also exert antiviral and anti-inflammatory effects, relieving organ damage and conferring a significant survival advantage to infected mice. Such a novel therapeutic agent can be readily manufactured into feasible treatment for COVID-19.