Levels of antibodies against the monkeypox virus compared by HIV status and historical smallpox vaccinations: a serological study.

Men who have sex with men and people living with HIV are disproportionately affected in the 2022 multi-country monkeypox epidemic. The smallpox vaccine can induce cross-reactive antibodies against the monkeypox virus (MPXV) and reduce the risk of infection. Data on antibodies against MPXV induced by historic smallpox vaccination in people with HIV are scarce. In this observational study, plasma samples were collected from people living with and without HIV in Shenzhen, China. We measured antibodies binding to two representative proteins of vaccinia virus (VACV; A27L and A33R) and homologous proteins of MPXV (A29L and A35R) using an enzyme-linked immunosorbent assay. We compared the levels of these antibodies between people living with and without HIV. Stratified analyses were performed based on the year of birth of 1981 when the smallpox vaccination was stopped in China. Plasma samples from 677 people living with HIV and 746 people without HIV were tested. A consistent pattern was identified among the four antibodies, regardless of HIV status. VACV antigen-reactive and MPXV antigen-reactive antibodies induced by historic smallpox vaccination were detectable in the people born before 1981, and antibody levels reached a nadir during or after 1981. The levels of smallpox vaccine-induced antibodies were comparable between people living with HIV and those without HIV. Our findings suggest that the antibody levels against MPXV decreased in both people living with and without HIV due to the cessation of smallpox vaccination.

Inverse relationship between HBV DNA levels and liver histopathological changes in immune-tolerant CHB patients.

Limited data exist regarding the association between hepatitis B virus (HBV) DNA levels and liver histopathological changes in patients with chronic hepatitis B (CHB) during the immune tolerant (IT) phase. In this study, we retrospectively analysed liver biopsy results from 150 adult IT-CHB patients. The liver tissue necroinflammation and fibrosis were evaluated by the Scheuer scoring system. Multivariate logistic regression, smooth curve fitting, and segmented regression models were used to examine the association between HBV DNA levels and liver histopathological changes. A total of 26%, 30.67% and 42% of IT patients had significant necroinflammation (≥G2), significant fibrosis (≥S2) and significant histopathological changes (≥G2 and/or ≥S2), respectively. HBV DNA levels were independently and non-linear inversely associated with significant necroinflammation and histopathological changes in IT-CHB patients. Patients with HBV DNA levels <107 IU/mL had a higher risk of significant histopathological changes compared to those with levels >107 IU/mL. The findings were further confirmed by smooth curve fitting analyses, subgroup and sensitivity analyses. In segmented regression model analyses, the optimal DNA value for the lowest odds ratio of significant histopathological changes was 7.26 log10 IU/mL. A non-linear inverse association between HBV DNA levels and significant histopathological changes in IT-CHB patients. DNA 7.26 log10 IU/mL may serve as a potential cut-off point to define a 'true immune tolerant phase' with minimal liver histopathological changes.

A signature based on circadian rhythm-associated genes for the evaluation of prognosis and the tumour microenvironment in HNSCC.

The morbidity and mortality rates of head and neck squamous cell carcinoma (HNSCC) remain high worldwide. Therefore, there is an urgent need to identify a new prognostic biomarker to guide the personalized treatment of HNSCC patients. Increasing evidence suggests that circadian rhythm genes play an important role in the development and progression of cancer. We aimed to explore the value of circadian rhythm genes in predicting prognosis and guiding the treatment of HNSCC. We first obtained a list of circadian rhythm genes from previous research. The sequencing data were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Finally, univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox proportional hazard analysis were performed to develop a prognostic signature (Circadian Rhythm-Related Gene Prognostic Index, CRRGPI) consisting of nine circadian rhythm genes. The signature exhibited good performance in predicting overall survival. Patients with low CRRGPI scores had lower metabolic activities and an active antitumour immunity ability. Additionally, a clinical cohort was used to further evaluate the ability of the CRRGPI to predict the efficacy of immune checkpoint inhibitors. In conclusion, the novel circadian rhythm-related gene signature can provide a precise prognostic evaluation with the potential capacity to guide individualized treatment regimens for HNSCC patients.

Whole-genome and genome-wide association studies improve key agricultural traits of safflower for industrial and medicinal use.

Safflower (Carthamus tinctorius) is widely cultivated around the world for its seeds and flowers. The presence of linoleic acid (LA) in its seeds and hydroxysafflor yellow A (HSYA) in its flowers are the crucial traits that enable safflower to be used for industrial and medicinal purposes. Understanding the genetic control of these traits is essential for optimizing the quality of safflower and its breeding. To further this research, we present a chromosome-scale assembly of the genome of the safflower variety 'Chuanhonghua 1', which was achieved using an integrated strategy combining Illumina, Oxford Nanopore, and Hi-C sequencing. We obtained a 1.17-Gb assembly with a contig N50 of 1.08 Mb, and all assembled sequences were assigned to 12 pseudochromosomes. Safflower's evolution involved the core eudicot γ-triplication event and a whole-genome duplication event, which led to large-scale genomic rearrangements. Extensive genomic shuffling has occurred since the divergence of the ancestor of dicotyledons. We conducted metabolite and transcriptome profiles with time- and part-dependent changes and screened candidate genes that significantly contribute to seed lipid biosynthesis. We also analyzed key gene families that participate in LA and HSYA biosynthesis. Additionally, we re-sequenced 220 safflower lines and carried out a genome-wide association study using high-quality SNP data for eight agronomic traits. We identified SNPs related to important traits in safflower. Besides, the candidate gene HH_034464 (CtCGT1) was shown to be involved in the biosynthesis of HSYA. Overall, we provide a high-quality reference genome and elucidate the genetic basis of LA and HSYA biosynthesis in safflower. This vast amount of data will benefit further research for functional gene mining and breeding in safflower.

Chromatin architecture of two different strains of Artemisia annua reveals the alterations in interaction and gene expression.

MAIN CONCLUSION: The hierarchical architecture of chromatins affects the gene expression level of glandular secreting trichomes and the artemisinin biosynthetic pathway-related genes, consequently bringing on huge differences in the content of artemisinin and its derivatives of A. annua. The plant of traditional Chinese medicine "Qinghao" is called Artemisia annua L. in Chinese Pharmacopoeia. High content and the total amount of artemisinin is the main goal of A. annua breeding, nevertheless, the change of chromatin organization during the artemisinin synthesis process has not been discovered yet. This study intended to find the roles of chromatin structure in the production of artemisinin through bioinformatics and experimental validation. Chromosome conformation capture analysis was used to scrutinize the interactions among chromosomes and categorize various scales of chromatin during artemisinin synthesis in A. annua. To confirm the effect of the changes in chromatin structure, Hi-C and RNA-sequencing were performed on two different strains to find the correlation between chromatin structure and gene expression levels on artemisinin synthesis progress and regulation. Our results revealed that the frequency of intra-chromosomal interactions was higher in the inter-chromosomal interactions between the root and leaves on a high artemisinin production strain (HAP) compared to a low artemisinin production strain (LAP). We found that compartmental transition was connected with interactions among different chromatins. Interestingly, glandular secreting trichomes (GSTs) and the artemisinin biosynthetic pathway (ABP) related genes were enriched in the areas which have the compartmental transition, reflecting the regulation of artemisinin synthesis. Topologically associated domain boundaries were associated with various distributions of genes and expression levels. Genes associated with ABP and GST in the adjacent loop were highly expressed, suggesting that epigenetic regulation plays an important role during artemisinin synthesis and glandular secreting trichomes production process. Chromatin structure could show an important status in the mechanisms of artemisinin synthesis process in A. annua.

Benefit of Nasal Douche in COVID-19 Patients with Recurrence of Positive SARS-CoV-2 Viral RNA.

Purpose: The purpose was to review relevant clinical data and formulate recommendations supporting the use of saline as a simple rinse for an early reassuring intervention to reduce the occurrence of re-positive COVID-19 patients. Methods: We conducted a single-centre retrospective cohort study, which enrolled patients with confirmed re-testing positive COVID-19 during 7-60 days after discharge from Third People's Hospital of Shenzhen. By one-to-two propensity score matching for age and sex, the control group of those not re-testing positive during the same period served as matched control. Results: A total of 223 patients were included in our study, 94 in re-positive group and 129 in non-re-positive group. The result shows that the rates of nasal douche treatment in the non-re-positive group were considerably higher than that of the re-positive group. And the Ct value of nasal douche group increased faster than that of non-nasal douche group after the Ct value reaching ≥35. Further analysis revealed that the higher the Ct value at the time of readmission, the shorter the time of average Ct values to reach ≥35. Conclusion: These findings suggest that nasal douche is beneficial to shorten the time of virus nucleic acid turning negative, thereby reducing the incidence of re-positive. The prevention and control of epidemics focuses on re-positive patients with Ct values <35.

Striking antibody evasion of SARS-CoV-2 Omicron sub-lineages BQ.1.1, XBB.1 and CH.1.1.

An intelligent indoor metasurface robotic is empowered on the physical layer by programmable metasurfaces and on the cyber layer by artificial-intelligence tools.

MOMS: A pipeline for scaffolding using multi-optical maps.

Here, we report a new multi-optical maps scaffolder (MOMS) aiming at utilizing complementary information among optical maps labelled by distinct enzymes. This pipeline was designed for data structure organization, scaffolding by path traversal, gap-filling and molecule reuse of optical maps. Our testing showed that this pipeline has uncapped enzyme tolerance in scaffolding. This means that there are no inbuilt limits as to the number of maps generated by different enzymes that can be utilized by MOMS. For the genome assembly of the human GM12878 cell line, MOMS significantly improved the contiguity and completeness with an up to 144-fold increase of scaffold N50 compared with initial assemblies. Benchmarking on the genomes of human and O. sativa showed that MOMS is more effective and robust compared with other optical-map-based scaffolders. We believe this pipeline will contribute to high-fidelity chromosome assembly and chromosome-level evolutionary analysis.

Breakthrough infection evokes the nasopharyngeal innate immune responses established by SARS-CoV-2-inactivated vaccine.

Nasopharyngeal immune responses are vital for defense against SARS-CoV-2 infection. Although vaccination via muscle immunization has shown a high efficacy in reducing severity and death in COVID-19 infection, breakthrough infection frequently happens because of mutant variants and incompletely established mucosal immunity, especially in the upper respiratory tract. Here, we performed a single-cell RNA and T-cell receptor repertoire sequencing and delineated a high-resolution transcriptome landscape of nasopharyngeal mucosal immune and epithelial cells in vaccinated persons with breakthrough infection and non-vaccinated persons with natural infection as control. The epithelial cells showed anti-virus gene expression diversity and potentially recruited innate immune cells into the nasopharyngeal mucous of vaccinated patients. Upon infection, they released significant pro-inflammatory cytokines and chemokines by macrophages and monocytes and expressed antigen-presenting relevant genes by dendritic cells. Such immune responses of nasopharyngeal innate immune cells would facilitate the strengthened expression of cytotoxic genes in virus-specific T-cell or B-cell differentiation into antibody-secreting cells at the early stage of breakthrough infection through cell interaction between innate and adaptive immune cells. Notably, these alterations of nasopharyngeal immune cells in breakthrough infection depended on the activated Nuclear factor-κB (NF-κB) and NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) signaling rather than type I interferon responses due to the general reduction in interferon-stimulated gene expression. Our findings suggest that vaccination potentially strengthens innate immune barriers and virus-specific memory immune cell responses, which could be quickly activated to defend against variant breakthrough infection and maintain nasopharyngeal epithelial cell integrity. Thus, this study highlights the necessity of a boost via nasal mucous after intramuscular immunization.

Genomic, transcriptomic, and epigenomic analysis of a medicinal snake, Bungarus multicinctus, to provides insights into the origin of Elapidae neurotoxins.

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of ß-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the ß-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

Infection with wild-type SARS-CoV-2 elicits broadly neutralizing and protective antibodies against omicron subvariants.

The omicron variants of SARS-CoV-2 have substantial ability to escape infection- and vaccine-elicited antibody immunity. Here, we investigated the extent of such escape in nine convalescent patients infected with the wild-type SARS-CoV-2 during the first wave of the pandemic. Among the total of 476 monoclonal antibodies (mAbs) isolated from peripheral memory B cells, we identified seven mAbs with broad neutralizing activity to all variants tested, including various omicron subvariants. Biochemical and structural analysis indicated the majority of these mAbs bound to the receptor-binding domain, mimicked the receptor ACE2 and were able to accommodate or inadvertently improve recognition of omicron substitutions. Passive delivery of representative antibodies protected K18-hACE2 mice from infection with omicron and beta SARS-CoV-2. A deeper understanding of how the memory B cells that produce these antibodies could be selectively boosted or recalled can augment antibody immunity against SARS-CoV-2 variants.

Omicron variants escape the persistent SARS-CoV-2-specific antibody response in 2-year COVID-19 convalescents regardless of vaccination.

With the ongoing COVID-19 pandemic and the emergence of various SARS-CoV-2 variants, a comprehensive evaluation of long-term efficacy of antibody response in convalescent individuals is urgently needed. Several longitudinal studies had reported the antibody dynamics after SARS-CoV-2 acute infection, but the follow-up was mostly limited to 1 year or 18 months at the maximum. In this study, we investigated the durability, potency, and susceptibility to immune evasion of SARS-CoV-2-specific antibody in COVID-19 convalescents for 2 years after discharge. These results showed the persistent antibody-dependent immunity could protect against the WT and Delta variant to some extent. However, the Omicron variants (BA.1, BA.2, and BA.4/5) largely escaped this preexisting immunity in recovered individuals. Furthermore, we revealed that inactivated vaccines (BBIBP-CorV, CoronaVac, or KCONVAC) could improve the plasma neutralization and help to maintain the broadly neutralizing antibodies at a certain level. Notably, with the time-dependent decline of antibody, 1-dose or 2-dose vaccination strategy seemed not to be enough to provide immune protection against the emerging variants. Overall, these results facilitated our understanding of SARS-CoV-2-induced antibody memory, contributing to the development of immunization strategy against SARS-CoV-2 variants for such a large number of COVID-19 survivors.

Neutralizing monoclonal antibody in patients with coronavirus disease 2019: an observational study.

BACKGROUND: Clinical data on patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta variant are limited, especially on clinical status after the application of antibody therapy. METHODS: We evaluated clinical status in patients with the SARS-CoV-2 delta variant after BRII-196 and BRII-198 treatment in an infectious disease hospital in China. We collected data on clinical symptoms, laboratory tests, radiological characteristics, viral load, anti-SARS-CoV-2 antibodies, treatment, and outcome. RESULTS: In mid-June 2021, 36 patients with delta variant infection were identified in Shenzhen. The most common symptoms at illness onset were cough (30.6%), fever (22.2%), myalgia (16.7%), and fatigue (16.7%). A small number of patients in this study had underlying diseases, including diabetes (5.6%) and hypertension (8.3%). The application of BRII-196 and BRII-198 can rapidly increase anti-SARS-CoV-2 IgG. The median peak IgG levels in the antibody treatment group were 32 times higher than those in the control group (P < 0.001). The time from admission to peak IgG levels in the antibody treatment group (mean: 10.2 days) was significantly shorter than that in the control group (mean: 17.7 days). Chest CT score dropped rapidly after antibody therapy, with a mean duration of 5.74 days from admission to peak levels. CONCLUSION: The results of this study suggest that the application of BRII-196 and BRII-198 antibody therapy improved clinical status in patients with SARS-CoV-2 delta variant infection.

Antigenic sin of wild-type SARS-CoV-2 vaccine shapes poor cross-neutralization of BA.4/5/2.75 subvariants in BA.2 breakthrough infections.

With declining SARS-CoV-2-specific antibody titers and increasing numbers of spike mutations, the ongoing emergence of Omicron subvariants causes serious challenges to current vaccination strategies. BA.2 breakthrough infections have occurred in people who have received the wild-type vaccines, including mRNA, inactivated, or recombinant protein vaccines. Here, we evaluate the antibody evasion of recently emerged subvariants BA.4/5 and BA.2.75 in two inactivated vaccine-immunized cohorts with BA.2 breakthrough infections. Compared with the neutralizing antibody titers against BA.2, marked reductions are observed against BA.2.75 in both 2-dose and 3-dose vaccine groups. In addition, although BA.2 breakthrough infections induce a certain cross-neutralization capacity against later Omicron subvariants, the original antigenic sin phenomenon largely limits the improvement of variant-specific antibody response. These findings suggest that BA.2 breakthrough infections seem unable to provide sufficient antibody protection against later subvariants such as BA.2.75 in the current immunization background with wild-type vaccines.

Healthy outcomes of patients with COVID-19 two years after the infection: a prospective cohort study.

The long-term effect of coronavirus disease 2019 (COVID-19) has been rarely known. This study aimed to investigate healthy outcomes of COVID-19 survivors up to 2 years after the infection. A total of 155 COVID-19 patients, who were discharged from Shenzhen Third People's Hospital from February 2020 to April 2020, were enrolled and followed up until March 4, 2022. COVID-19 survivors received questionnaires of long COVID symptoms and psychological symptoms, pulmonary function tests, chest computed tomography (CT) scans and routine laboratory tests. Two years after infection, 36.6% of patients had at least one symptom of long COVID. Vision impairment and fatigue were the most common symptom. 35.0% of participants still had at least one psychological symptom of anxiety, depression, post-traumatic stress symptoms, and sleep difficulties. Radiographic abnormalities were presented in 50.7% of patients, with the most common features of fibrosis-like lesions and residual ground-glass opacity. Diffuse dysfunction (24.0%) was the main abnormalities of pulmonary function tests. Most laboratory parameters returned to normal range, while persistent abnormalities in kidney and liver function test were observed in a subset of participants after discharge. Two years after COVID-19 infection, persistent symptoms of long COVID and psychological symptoms, as well as abnormalities in pulmonary function tests and CT, were still common in a subset of recovering individuals. These findings were limited by the lack of a healthy control group and pre-COVID assessments, which should be confirmed by further large-scale studies.

Clinical status of patients 1 year after hospital discharge following recovery from COVID-19: a prospective cohort study.

BACKGROUND: The long-term clinical status of coronavirus disease 2019 (COVID-19) in recovered patients remains largely unknown. This prospective cohort study evaluated clinical status of COVID-19 and explored the associated risk factors. METHODS: At the outpatient visit, patients underwent routine blood tests, physical examinations, pulmonary function tests, 6-min walk test, high-resolution computed tomography (CT) of the chest, and extrapulmonary organ function tests. RESULTS: 230 patients were analyzed. Half (52.7%) reported at least one symptom, most commonly fatigue (20.3%) and sleep difficulties (15.8%). Anxiety (8.2%), depression (11.3%), post-traumatic symptoms (10.3%), and sleep disorders (26.3%) were also reported. Diffusion impairments were found in 35.4% of the patients. Abnormal chest CT scans were present in 63.5% of the patients, mainly reticulation and ground-glass opacities. Further, a persistent decline in kidney function was observed after discharge. SARS-CoV-2-specific antibodies of IgA, IgG, and IgM were positive in 56.4%, 96.3%, and 15.2% of patients, respectively. Multivariable logistic regression showed that disease severity, age, and sex were closely related to patient recovery. CONCLUSIONS: One year after hospital discharge, patients recovered from COVID-19 continued to experience both pulmonary and extrapulmonary dysfunction. While paying attention to pulmonary manifestations of COVID-19, follow-up studies on extrapulmonary manifestations should be strengthened.

Clinical Predictors of Functional Cure in Children 1-6 Years-old with Chronic Hepatitis B.

Background and Aims: Hepatitis B surface antigen (HBsAg) clearance is significantly more common in children with chronic hepatitis B (CHB) than in adults; however, the possible influencing factors related to HBsAg loss have yet to be found. This study aimed to explore the efficacy of long-term interferon (IFN)α therapy in treating children with CHB and analyzed the factors influencing functional cure after treatment. Methods: A total of 236 children aged 1-6 years and diagnosed with CHB via liver biopsy were included in the study, all receiving IFNα treatment (IFNα-2b monotherapy, IFNα-2b followed by lamivudine [LAM] or IFNα-2b combined with LAM) and followed up for 144 weeks. A comprehensive analysis was conducted on clinical data, including biochemical items, serum markers of hepatitis B virus (HBV) and immunological indexes, and logistic regression analysis was used to screen the influencing factors related to HBsAg loss. Results: The cumulative loss rates of HBsAg were 79.5%, 62.1% and 42.1% at 144 weeks after the start of treatment in the 1-3 years-old group, 3-5 years-old group and 5-7 years-old group, respectively (p<0.05). IFNα-2b combined with LAM treatment displayed the highest HBsAg loss rates compared with monotherapy and sequential treatment (p=0.011). Younger baseline age and lower HBsAg levels were independent factors for the prediction of HBsAg loss (p<0.05). The baseline PreS1 and hepatitis B core antibody levels in the HBsAg loss group were lower than those in the HBsAg non-loss group. In addition, the PreS1 level was positively corelated with the level of HBsAg, HBV DNA and liver inflammation. Conclusions: Long-term treatment with IFNα was effective in achieving HBsAg loss in CHB children aged 1-6 years-old. Age less than 3 years-old and lower HBsAg levels are independent predictors of functional cure in children with CHB.