Construction of SNP fingerprint and population genetic analysis of honeysuckle germplasm resources in China

Introduction The flower buds of Lonicera japonica Thunb. are widely used in Chinese medicine for their anti-inflammatory properties, and they have played an important role in the fight against SARS COVID-19 and other major epidemics. However, due to the lack of scientific and accurate variety identification methods and national unified standards, scattered and non-standardized management in flower bud production has led to mixed varieties that have caused significant difficulties in the cataloging and preservation of germplasm resources and the identification, promotion, and application of new L. japonica varieties. Methods In this study, we evaluated the population structure, genetic relationships, and genetic fingerprints of 39 germplasm resources of Lonicera in China using simplified genome sequencing technology. Results A total of 13,143,268 single nucleotide polymorphisms (SNPs) were identified. Thirty-nine samples of Lonicera were divided into four subgroups, and the population structure and genetic relationships among existing Lonicera germplasm resources were determined using principal component analysis, population structure analysis, and phylogenetic tree analysis. Through several stringent selection criteria, 15 additional streamlined, high-quality DNA fingerprints were filtered out of the validated 50 SNP loci and verified as being able to effectively identify the 39 Lonicera varieties. Discussion To our knowledge, this is the first comprehensive study measuring the diversity and population structure of a large collection of Lonicera varieties in China. These results have greatly broadened our understanding of the diversity, phylogeny, and population structure of Lonicera. The results may enhance the future analysis of genetic diversity, species identification, property rights disputes, and molecular breeding by providing a scientific basis and reference data for these efforts.

[Glycosylation, glycan receptors recognition of SARS-CoV-2 and discoveries of glycan inhibitors against SARS-CoV-2].

COVID-19 represents the most serious public health event in the past few decades of the 21st century. The development of vaccines, neutralizing antibodies, and small molecule chemical agents have effectively prevented the rapid spread of COVID-19. However, the continued emergence of SARS-CoV-2 variants have weakened the efficiency of these vaccines and antibodies, which brought new challenges for searching novel anti-SARS-CoV-2 drugs and methods. In the process of SARS-CoV-2 infection, the virus firstly attaches to heparan sulphate on the cell surface of respiratory tract, then specifically binds to hACE2. The S protein of SARS-CoV-2 is a highly glycosylated protein, and glycosylation is also important for the binding of hACE2 to S protein. Furthermore, the S protein is recognized by a series of lectin receptors in host cells. These finding implies that glycosylation plays important roles in the invasion and infection of SARS-CoV-2. Based on the glycosylation pattern and glycan recognition mechanisms of SARS-CoV-2, it is possible to develop glycan inhibitors against COVID-19. Recent studies have shown that sulfated polysaccharides originated from marine sources, heparin and some other glycans display anti-SARS-CoV-2 activity. This review summarized the function of glycosylation of SARS-CoV-2, discoveries of glycan inhibitors and the underpinning molecular mechanisms, which will provide guidelines to develop glycan-based new drugs against SARS-CoV-2.

Structural and Biochemical Analysis Reveals Catalytic Mechanism of Fucoidan Lyase from Flavobacterium sp. SA-0082.

Fucoidans represent a type of polyanionic fucose-containing sulfated polysaccharides (FCSPs) that are cleaved by fucoidan-degrading enzymes, producing low-molecular-weight fucoidans with multiple biological activities suitable for pharmacological use. Most of the reported fucoidan-degrading enzymes are glycoside hydrolases, which have been well studied for their structures and catalytic mechanisms. Little is known, however, about the rarer fucoidan lyases, primarily due to the lack of structural information. FdlA from Flavobacterium sp. SA-0082 is an endo-type fucoidan-degrading enzyme that cleaves the sulfated fuco-glucuronomannan (SFGM) through a lytic mechanism. Here, we report nine crystal structures of the catalytic N-terminal domain of FdlA (FdlA-NTD), in both its wild type (WT) and mutant forms, at resolutions ranging from 1.30 to 2.25 Å. We show that the FdlA-NTD adopts a right-handed parallel ß-helix fold, and possesses a substrate binding site composed of a long groove and a unique alkaline pocket. Our structural, biochemical, and enzymological analyses strongly suggest that FdlA-NTD utilizes catalytic residues different from other ß-helix polysaccharide lyases, potentially representing a novel polysaccharide lyase family.

Novel Insights Into the Sulfated Glucuronic Acid-Based Anti-SARS-CoV-2 Mechanism of Exopolysaccharides From Halophilic Archaeon Haloarcula hispanica.

The pandemic caused by SARS-CoV-2 is the most widely spread disease in the 21st century. Due to the continuous emergence of variants across the world, it is necessary to expand our understanding of host-virus interactions and explore new agents against SARS-CoV-2. In this study, it was found exopolysaccharides (EPSs) from halophilic archaeon Haloarcula hispanica ATCC33960 can bind to the spike protein of SARS-CoV-2 with the binding constant KD of 2.23 nM, block the binding of spike protein to Vero E6 and bronchial epithelial BEAS-2B cells, and inhibit pseudovirus infection. However, EPSs from the gene deletion mutant △HAH_1206 almost completely lost the antiviral activity against SARS-CoV-2. A significant reduction of glucuronic acid (GlcA) and the sulfation level in EPSs of △HAH_1206 was clearly observed. Our results indicated that sulfated GlcA in EPSs is possible for a main structural unit in their inhibition of binding of SARS-CoV-2 to host cells, which would provide a novel antiviral mechanism and a guide for designing new agents against SARS-CoV-2.

Willingness of Chinese Men Who Have Sex With Men to Use Smartphone-Based Electronic Readers for HIV Self-testing: Web-Based Cross-sectional Study.

BACKGROUND: The need for strategies to encourage user-initiated reporting of results after HIV self-testing (HIVST) persists. Smartphone-based electronic readers (SERs) have been shown capable of reading diagnostics results accurately in point-of-care diagnostics and could bridge the current gaps between HIVST and linkage to care. OBJECTIVE: Our study aimed to assess the willingness of Chinese men who have sex with men (MSM) in the Jiangsu province to use an SER for HIVST through a web-based cross-sectional study. METHODS: From February to April 2020, we conducted a convenience web-based survey among Chinese MSM by using a pretested structured questionnaire. Survey items were adapted from previous HIVST feasibility studies and modified as required. Prior to answering reader-related questions, participants watched a video showcasing a prototype SER. Statistical analysis included descriptive analysis, chi-squared test, and multivariable logistic regression. P values less than .05 were deemed statistically significant. RESULTS: Of 692 participants, 369 (53.3%) were aged 26-40 years, 456 (65.9%) had ever self-tested for HIV, and 493 (71.2%) were willing to use an SER for HIVST. Approximately 98% (483/493) of the willing participants, 85.3% (459/538) of ever self-tested and never self-tested, and 40% (46/115) of unwilling participants reported that SERs would increase their HIVST frequency. Engaging in unprotected anal intercourse with regular partners compared to consistently using condoms (adjusted odds ratio [AOR] 3.04, 95% CI 1.19-7.74) increased the odds of willingness to use an SER for HIVST. Participants who had ever considered HIVST at home with a partner right before sex compared to those who had not (AOR 2.99, 95% CI 1.13-7.90) were also more willing to use an SER for HIVST. Playing receptive roles during anal intercourse compared to playing insertive roles (AOR 0.05, 95% CI 0.02-0.14) was associated with decreased odds of being willing to use an SER for HIVST. The majority of the participants (447/608, 73.5%) preferred to purchase readers from local Centers of Disease Control and Prevention offices and 51.2% (311/608) of the participants were willing to pay less than US $4.70 for a reader device. CONCLUSIONS: The majority of the Chinese MSM, especially those with high sexual risk behaviors, were willing to use an SER for HIVST. Many MSM were also willing to self-test more frequently for HIV with an SER. Further research is needed to ascertain the diagnostic and real-time data-capturing capacity of prototype SERs during HIVST.

Evaluation of Prognosis of Coma Patients With Acute Brain Injury by Electroencephalogram Bispectral Index Monitoring.

BACKGROUND: The high mortality rate of comatose patients with traumatic brain injury is a prominent public health issue that negatively impacts patients and their families. Objective, reliable tools are needed to guide treatment decisions and prioritize resources. OBJECTIVE: This study aimed to evaluate the prognostic value of the bispectral index (BIS) in comatose patients with severe brain injury. METHODS: This was a retrospective cohort study of 84 patients with severe brain injury and Glasgow Coma Scale (GCS) scores of 8 and less treated from January 2015 to June 2017. Sedatives were withheld at least 24 hr before BIS scoring. The BIS value, GCS scores, and Full Outline of UnResponsiveness (FOUR) were monitored hourly for 48 hr. Based on the Glasgow Outcome Scale (GOS) score, the patients were divided into poor (GOS score: 1-2) and good prognosis groups (GOS score: 3-5). The correlation between BIS and prognosis was analyzed by logistic regression, and the receiver operating characteristic curves were plotted. RESULTS: The mean (SD) of the BIS value: 54.63 (11.76), p = .000; and GCS score: 5.76 (1.87), p = .000, were higher in the good prognosis group than in the poor prognosis group. Lower BIS values and GCS scores were correlated with poorer prognosis. Based on the area under the curve of receiver operating characteristic curves, the optimal diagnostic cutoff value of the BIS was 43.6, and the associated sensitivity and specificity were 85.4% and 74.4%, respectively. CONCLUSION: Taken together, our study indicates that BIS had good predictive value on prognosis. These findings suggested that BIS could be used to evaluate the severity and prognosis of severe brain injury.

Clinical significance and molecular mechanism of angiotensin-converting enzyme 2 in hepatocellular carcinoma tissues.

During the pandemic of the coronavirus disease 2019, there exist quite a few studies on angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 infection, while little is known about ACE2 in hepatocellular carcinoma (HCC). The detailed mechanism among ACE2 and HCC still remains unclear, which needs to be further investigated. In the current study with a total of 6,926 samples, ACE2 expression was downregulated in HCC compared with non-HCC samples (standardized mean difference = -0.41). With the area under the curve of summary receiver operating characteristic = 0.82, ACE2 expression showed a better ability to differentiate HCC from non-HCC. The mRNA expression of ACE2 was related to the age, alpha-fetoprotein levels and cirrhosis of HCC patients, and it was identified as a protected factor for HCC patients via Kaplan-Meier survival, Cox regression analyses. The potential molecular mechanism of ACE2 may be relevant to catabolic and cell division. In all, decreasing ACE2 expression can be seen in HCC, and its protective role for HCC patients and underlying mechanisms were explored in the study.

Antiviral Drug Delivery System for Enhanced Bioactivity, Better Metabolism and Pharmacokinetic Characteristics.

Antiviral drugs (AvDs) are the primary resource in the global battle against viruses, including the recent fight against corona virus disease 2019 (COVID-19). Most AvDs require multiple medications, and their use frequently leads to drug resistance, since they have poor oral bioavailability and low efficacy due to their low solubility/low permeability. Characterizing the in vivo metabolism and pharmacokinetic characteristics of AvDs may help to solve the problems associated with AvDs and enhance their efficacy. In this review of AvDs, we systematically investigated their structure-based metabolic reactions and related enzymes, their cellular pharmacology, and the effects of metabolism on AvD pharmacodynamics and pharmacokinetics. We further assessed how delivery systems achieve better metabolism and pharmacology of AvDs. This review suggests that suitable nanosystems may help to achieve better pharmacological activity and pharmacokinetic behavior of AvDs by altering drug metabolism through the utilization of advanced nanotechnology and appropriate administration routes. Notably, such AvDs as ribavirin, remdesivir, favipiravir, chloroquine, lopinavir and ritonavir have been confirmed to bind to the severe acute respiratory syndrome-like coronavirus (SARS-CoV-2) receptor and thus may represent anti-COVID-19 treatments. Elucidating the metabolic and pharmacokinetic characteristics of AvDs may help pharmacologists to identify new formulations with high bioavailability and efficacy and help physicians to better treat virus-related diseases, including COVID-19.

The impact of disruptions due to COVID-19 on HIV transmission and control among men who have sex with men in China.

INTRODUCTION: The COVID-19 pandemic is impacting HIV care globally, with gaps in HIV treatment expected to increase HIV transmission and HIV-related mortality. We estimated how COVID-19-related disruptions could impact HIV transmission and mortality among men who have sex with men (MSM) in four cities in China, over a one- and five-year time horizon. METHODS: Regional data from China indicated that the number of MSM undergoing facility-based HIV testing reduced by 59% during the COVID-19 pandemic, alongside reductions in ART initiation (34%), numbers of all sexual partners (62%) and consistency of condom use (25%), but initial data indicated no change in viral suppression. A mathematical model of HIV transmission/treatment among MSM was used to estimate the impact of disruptions on HIV infections/HIV-related deaths. Disruption scenarios were assessed for their individual and combined impact over one and five years for 3/4/6-month disruption periods, starting from 1 January 2020. RESULTS: Our model predicted new HIV infections and HIV-related deaths would be increased most by disruptions to viral suppression, with 25% reductions (25% virally suppressed MSM stop taking ART) for a three-month period increasing HIV infections by 5% to 14% over one year and deaths by 7% to 12%. Observed reductions in condom use increased HIV infections by 5% to 14% but had minimal impact (<1%) on deaths. Smaller impacts on infections and deaths (<3%) were seen for disruptions to facility HIV testing and ART initiation, but reduced partner numbers resulted in 11% to 23% fewer infections and 0.4% to 1.0% fewer deaths. Longer disruption periods (4/6 months) amplified the impact of disruption scenarios. When realistic disruptions were modelled simultaneously, an overall decrease in new HIV infections occurred over one year (3% to 17%), but not for five years (1% increase to 4% decrease), whereas deaths mostly increased over one year (1% to 2%) and five years (1.2 increase to 0.3 decrease). CONCLUSIONS: The overall impact of COVID-19 on new HIV infections and HIV-related deaths is dependent on the nature, scale and length of the various disruptions. Resources should be directed to ensuring levels of viral suppression and condom use are maintained to mitigate any adverse effects of COVID-19-related disruption on HIV transmission and control among MSM in China.

Nucleic acid detection results analysis in different COVID-19 samples

Objective: To understand the results and influencing factors of SARS-CoV-2 nucleic acid detection among specimens in different types and stages of coronavirus disease 2019 (COVID-19) progression.

Internet search data could Be used as novel indicator for assessing COVID-19 epidemic.

The pandemic of the coronavirus disease (COVID-19) poses a huge challenge all countries, since no one is well prepared for it. To be better prepared for future pandemics, we evaluated association between the internet search data with reported COVID-19 cases to verify whether it could become an early indicator for emerging epidemic. After the keyword filtering and Index composition, we found that there were close correlations between Composite Index and suspected cases for COVID-19 (r = 0.921, P < 0.05). The Search Index was applied for the Autoregressive Integrated Moving Average with Exogenous Variables (ARIMAX) model to quantify the relationship. Compared with the model based on surveillance data only, the ARIMAX model had smaller Akaike Information Criterion (AIC = 403.51) and the most accurate predictive values. Overall, the Internet search data could serve as a convenient indicator for predicting the epidemic and to monitor its trends.