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With the escalating incidence and mortality rates of cancer, there is an ever-growing emphasis on the research of anticancer drugs. Cordycepin, the primary nucleoside antibiotic isolated from Cordyceps militaris, has emerged as a remarkable agent for cancer prevention and treatment. Functioning as a natural targeted antitumor drug, cordycepin assumes an increasingly pivotal role in cancer therapy. This review elucidates the mechanisms of cordycepin in inhibiting tumor cell proliferation, inducing apoptosis, as well as its capabilities in suppressing angiogenesis and metastasis. Moreover, the immunomodulatory effects of cordycepin in cancer treatment are explored. Additionally, the current status, challenges, and future prospects of cordycepin application in clinical trials are briefly discussed. The objective is to provide a valuable reference for the utilization of cordycepin in cancer treatment.
Subject(s)
Apoptosis , Cell Proliferation , Deoxyadenosines , Neoplasms , Deoxyadenosines/pharmacology , Deoxyadenosines/therapeutic use , Humans , Neoplasms/drug therapy , Cell Proliferation/drug effects , Apoptosis/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Neovascularization, Pathologic/drug therapyABSTRACT
Previous studies reveal that psoriatic arthritis (PsA) and ankylosing spondylitis (AS) share susceptibility genes, such as HLA-B27, demonstrating a degree of genetic overlap between these diseases. Recent studies have identified a number of novel AS and PsA genetic susceptibility loci, but data on these loci in Chinese PsA patients are limited. To identify candidate genes that confer susceptibility to PsA in Chinese patients with PsA, psoriasis vulgaris (PsV), and healthy controls. Sixteen susceptibility loci, reported in a genome-wide association study of AS, and nine susceptibility loci, reported in candidate gene studies of PsA, were examined. Single-nucleotide polymorphisms (SNPs) were genotyped in 503 patients with PsA, 496 patients with PsV, and 979 healthy controls using the SNPscanTM multiplex SNP genotyping platform. PLINK software and logistic regression analysis were used to estimate the statistical significance of associations. PPP2R3C (rs8006884) was shown to significantly associate with PsA+PsV (p = 1.92×10-3, OR = 1.28) and was suggested to associate with PsV (p = 0.03, OR = 1.19). A suggestive association was also observed between IL-23R (rs12141575) and PsA as well as with axial PsA based on subtype analysis, KIF3A (rs2897442) and PsV, and ERN1 (rs196941) or IFIH1 (rs984971) and axial PsA. Our results suggest that PPP2R3C confers susceptibility to PsA and PsV, and that this gene may be related to the pathogenesis of psoriatic lesions and arthritis. Moreover, our results indicate a possible association between IL-23R, ERN1, or IFIH1 and subtypes of PsA, and between KIF3A and PsV.
Subject(s)
Arthritis, Psoriatic , Asian People , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Spondylitis, Ankylosing , Humans , Arthritis, Psoriatic/genetics , Spondylitis, Ankylosing/genetics , Male , Female , Asian People/genetics , Adult , Middle Aged , Case-Control Studies , China , Receptors, Interleukin/genetics , Protein Phosphatase 2/genetics , Genotype , Genome-Wide Association Study , Psoriasis/genetics , East Asian PeopleABSTRACT
With the escalating incidence and mortality rates of cancer, there is an ever-growing emphasis on the research of anticancer drugs. Cordycepin, the primary nucleoside antibiotic isolated from Cordyceps militaris, has emerged as a remarkable agent for cancer prevention and treatment. Functioning as a natural targeted antitumor drug, cordycepin assumes an increasingly pivotal role in cancer therapy. This review elucidates the mechanisms of cordycepin in inhibiting tumor cell proliferation, inducing apoptosis, as well as its capabilities in suppressing angiogenesis and metastasis. Moreover, the immunomodulatory effects of cordycepin in cancer treatment are explored. Additionally, the current status, challenges, and future prospects of cordycepin application in clinical trials are briefly discussed. The objective is to provide a valuable reference for the utilization of cordycepin in cancer treatment.
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The number of elderly patients with aneurysmal subarachnoid hemorrhage (aSAH) is increasing annually. The prognostic nutritional index (PNI) is used as a novel and valuable prognostic marker for various neoplastic diseases and other critical illnesses. This study aimed to identify the short-term prognostic value of preoperative PNI in elderly patients who underwent neurosurgical clipping for aSAH. This retrospective study included elderly patients with aSAH who underwent neurosurgical clipping from January 2018 to December 2020. Clinical variables and 6-month outcomes were collected and compared. Epidemiological data and effect factors of prognosis were evaluated. Multivariate logistic regression and receiver operating characteristics (ROC) curve analyses were used to evaluate the predictive value of preoperative PNI. Multiple logistic regression was performed to establish a nomogram. A total of 124 elderly patients were enrolled. Multivariate logistic regression analysis showed that preoperative PNI (odds ratio (OR), 0.779; 95% confidence interval (CI), 0.689-0.881; P < 0.001), Hunt-Hess grade (OR, 3.291; 95%CI, 1.816-5.966; P < 0.001), and hydrocephalus (OR, 9.423; 95%CI, 2.696-32.935; P < 0.001) were significant predictors. The area under the ROC curve of PNI was 0.829 (95% CI, 0.755-0.903; P < 0.001) with a sensitivity and specificity of 68.4% and 83.3%, respectively, and the cutoff value was 46.36. Patients with preoperative PNI of < 46.36 had a significantly unfavorable 6-months prognosis (F = 40.768, P < 0.001). Preoperative PNI is independently correlated with the 6-month prognosis in elderly patients who undergo neurosurgical clipping for aSAH.
Subject(s)
Subarachnoid Hemorrhage , Humans , Aged , Prognosis , Subarachnoid Hemorrhage/surgery , Nutrition Assessment , Retrospective Studies , NomogramsABSTRACT
Exercise-induced perturbation of skeletal muscle metabolites is a probable mediator of long-term health benefits in older adults. Although specific metabolites have been identified to be impacted by age, physical activity and exercise, the depth of coverage of the muscle metabolome is still limited. Here, we investigated resting and exercise-induced metabolite distribution in muscle from well-phenotyped older adults who were active or sedentary, and a group of active young adults. Percutaneous biopsies of the vastus lateralis were obtained before, immediately after and 3 h following a bout of endurance cycling. Metabolite profile in muscle biopsies was determined by tandem mass spectrometry. Mitochondrial energetics in permeabilized fibre bundles was assessed by high resolution respirometry and fibre type proportion was assessed by immunohistology. We found that metabolites of the kynurenine/tryptophan pathway were impacted by age and activity. Specifically, kynurenine was elevated in muscle from older adults, whereas downstream metabolites of kynurenine (kynurenic acid and NAD+ ) were elevated in muscle from active adults and associated with cardiorespiratory fitness and muscle oxidative capacity. Acylcarnitines, a potential marker of impaired metabolic health, were elevated in muscle from physically active participants. Surprisingly, despite baseline group difference, acute exercise-induced alterations in whole-body substrate utilization, as well as muscle acylcarnitines and ketone bodies, were remarkably similar between groups. Our data identified novel muscle metabolite signatures that associate with the healthy ageing phenotype provoked by physical activity and reveal that the metabolic responsiveness of muscle to acute endurance exercise is retained [NB]:AUTHOR: Please ensure that the appropriate material has been provide for Table S2, as well as for Figures S1 to S7, as also cited in the text with age regardless of activity levels. KEY POINTS: Kynurenine/tryptophan pathway metabolites were impacted by age and physical activity in human muscle, with kynurenine elevated in older muscle, whereas downstream products kynurenic acid and NAD+ were elevated in exercise-trained muscle regardless of age. Acylcarnitines, a marker of impaired metabolic health when heightened in circulation, were elevated in exercise-trained muscle of young and older adults, suggesting that muscle act as a metabolic sink to reduce the circulating acylcarnitines observed with unhealthy ageing. Despite the phenotypic differences, the exercise-induced response of various muscle metabolite pools, including acylcarnitine and ketone bodies, was similar amongst the groups, suggesting that older adults can achieve the metabolic benefits of exercise seen in young counterparts.
Subject(s)
Kynurenine , Tryptophan , Young Adult , Humans , Aged , Kynurenine/metabolism , Tryptophan/metabolism , Kynurenic Acid , NAD/metabolism , Muscle, Skeletal/physiology , Exercise/physiologyABSTRACT
AIM To analyze saponins from Panacis Quinquefolii Radix of different regions(Jilin,Liaoning,Heilongjiang,Shandong)based on UHPLC-Q-Orbitrap/MS technology.METHODS Panacis Quinquefolii Radix had its saponins qualitatively analyzed by UHPLC-Q-Orbitrap/MS;and its differential saponins revealing different regions screened by the principal component analysis,orthogonal partial least squares discriminant analysis and differential component analysis.RESULTS A total of 62 saponins were identified;saponin variations due to the growth areas verified by the principal component analysis;and 28 differential saponins including 13 protopanaxadiol,6 protopanaxatriol,4 oleanolane,2 oxytetracycline,and 3 C-17 side chain variants further screened by orthogonal partial least-squares discriminant analysis model.The relative contents of protopanaxadiol-type and protopanaxatriol-type saponins in the four producing areas reduced following the order of Liaoning,Jilin,Heilongjiang,and Shandong.CONCLUSION This simple,accurate and efficient method provides a theoretical basis for the quality evaluation of Panacis Quinquefolii Radix.
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Objective:To explore the characteristics of functional connectivity (FC) and regional spontaneous brain activity in patients in a minimally-conscious state (MCS).Methods:Resting-state functional near-infrared spectroscopy (rs-fNIRS) was used. Ten minimally-conscious patients were studied along with 12 healthy counterparts as healthy controls (HC). Five minutes of rs-fNIRS data were recorded from each subject and FC and the fractional amplitude of low-frequency fluctuations (fALFFs) of 53 channels were computed using the NIRS-KIT toolbox. The results were compared between the two groups.Results:Compared with the HC group, a significant decrease was observed in the average FC strength of seventeen channel pairs after false discovery rate (FDR) correction. Most were in the right and left frontal pole, as well as the dorsolateral prefrontal lobe. Compared with the HC group, the average fALFF values of Broca′s area (channel 2), the premotor cortex and the supplementary motor cortex (channels 4, 10, and 40), the dorsolateral prefrontal lobe (channels 6, 11, 25, 39), the eye motor area of the frontal lobe (channel 12) and the frontal pole (channels 23, 27, 36) were significantly greater in the MCS group. The fluctuations of the frontal pole (channel 19) were significantly less (after FDR correction).Conclusion:In an MCS spontaneous neural activity is over-active in the prefrontal lobe and some speech- and motor-related brain regions, and coordination of the internal prefrontal functional network is disordered.
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Glaucoma is a chronic optic neuropathy that affects the retinal ganglion cells, characterized by optic disc atrophy, visual field defects, and visual acuity loss. Since glaucoma is a chronic disease, long-term use of topical intraocular pressure-lowering medications often leads to ocular surface diseases, thus reducing medication adherence and ultimately affecting treatment efficacy. Currently, topical intraocular pressure-lowering medications include prostaglandin derivatives, β-adrenergic blockers, α-adrenergic agonists, topical carbonic anhydrase inhibitors, and cholinergic drugs. This article provides a comprehensive review of the effects and related mechanisms of these five antiglaucoma medications on the ocular surface of glaucoma patients and offers preventative measures for the protection of ocular surface in glaucoma patients.
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Objective: To understand the genotype distribution and transmission pattern of rubella virus (RuV) circulating in Yunnan Province. Methods: Throat swab samples were collected from rubella outbreaks and sporadic cases in nine prefectures/cities of Yunnan Province from 2011 to 2021. Virus isolation, amplification of target genes and sequence determination were performed on the RuV-positive samples. The genotypes and lineages of Yunnan strains were determined by comparing them with the reference strains, and further phylogenetic analysis was performed with Yunnan strains and strains circulating in other provinces of China during the same period. Results: RuV circulating in Yunnan province during 2011-2021 showed significant genetic diversity, and three lineages, 1E-L1, 2B-L1 and 1E-L2, were detected. Two lineage-switches were also identified, including the conversion of 1E-L1 to 2B-L1 between 2012 and 2013, and the replacement of 2B-L1 to 1E-L2 after 2018. The time of the switches was basically consistent with the outbreak in Yunnan province in 2012 and the time of the rubella reemergence and epidemic between 2018 and 2019. The amino acid sequence of RuV virus strains in Yunnan province was highly conserved, and no important functional regions were changed. Conclusions: The transmission pattern of RuV in Yunnan province is generally consistent with the epidemic trend of RuV in other provinces of China.
Subject(s)
Humans , Rubella virus/genetics , Phylogeny , China/epidemiology , Rubella/epidemiology , GenotypeABSTRACT
Objective: To understand the genotype distribution and transmission pattern of rubella virus (RuV) circulating in Yunnan Province. Methods: Throat swab samples were collected from rubella outbreaks and sporadic cases in nine prefectures/cities of Yunnan Province from 2011 to 2021. Virus isolation, amplification of target genes and sequence determination were performed on the RuV-positive samples. The genotypes and lineages of Yunnan strains were determined by comparing them with the reference strains, and further phylogenetic analysis was performed with Yunnan strains and strains circulating in other provinces of China during the same period. Results: RuV circulating in Yunnan province during 2011-2021 showed significant genetic diversity, and three lineages, 1E-L1, 2B-L1 and 1E-L2, were detected. Two lineage-switches were also identified, including the conversion of 1E-L1 to 2B-L1 between 2012 and 2013, and the replacement of 2B-L1 to 1E-L2 after 2018. The time of the switches was basically consistent with the outbreak in Yunnan province in 2012 and the time of the rubella reemergence and epidemic between 2018 and 2019. The amino acid sequence of RuV virus strains in Yunnan province was highly conserved, and no important functional regions were changed. Conclusions: The transmission pattern of RuV in Yunnan province is generally consistent with the epidemic trend of RuV in other provinces of China.
Subject(s)
Humans , Rubella virus/genetics , Phylogeny , China/epidemiology , Rubella/epidemiology , GenotypeABSTRACT
Background: Previous studies demonstrated a controversial relationship between sarcopenia (SP) and osteoarthritis (OA) and their genetic causality is unclear. Thus, we conducted a Mendelian randomization (MR) analysis to evaluate the possible causal association between sarcopenia-related traits (appendicular lean mass (ALM), grip strength, usual walking pace) and OA. Method: We used pooled genetic data from the UK Biobank for ALM(n = 450,243), left-hand grip strength (n = 461,026), right-hand grip strength (n = 461,089) and usual walking pace (n = 459,915). Moreover, summary statistics for OA were obtained from the latest study conducted by the Genetics of Osteoarthritis Consortium, including all OA (n = 826,690), hand OA (n = 303,7782), hip OA (n = 353,388) and knee OA (n = 396,054). The primary method for estimating causal effects was the inverse-variance weighted (IVW) method, with the utilizing of false discovery rate adjusted p values (P FDR). Additional MR methods such as MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), weighted median were employed as supplementary analyses. Results: We discovered ALM (odds ratio (OR) = 1.103, 95% confidence interval (CI) = 1.052-1.156, P FDR = 2.87E-04), hand grip strength (left, IVW OR = 0.823, 95% CI = 0.712 to 0.952, P FDR = 0.020; right, OR = 0.826, 95% CI = 0.718 to 0.950, P FDR = 0.020), and usual walking pace (OR = 0.339, 95% CI = 0.204 to 0.564, P FDR = 2.38E-04) were causally associated with OA risk. In the reverse MR analysis, we identified a causal effect of OA on ALM (ß = -0.258, 95% CI = -0.369 to 0.146, P FDR = 0.6.07E-06), grip strength (left, ß = -0.064, 95% CI = -0.104 to 0.024, P FDR = 0.002; right, ß = -0.055, 95% CI = -0.095 to 0.014, P FDR = 0.008), and usual walking pace (ß = -0.104, 95% CI = -0.147 to 0.061, P FDR = 1.61E-05). Conclusion: This present study suggests an obvious causality of SP on OA, with condition exhibiting site-specific effects, while evidence was also provided for the causal effect of OA on SP.
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Cellular immune defects associated with suboptimal responses to SARS-CoV-2 mRNA vaccination in people receiving hemodialysis (HD) are poorly understood. We longitudinally analyzed antibody, B cell, CD4+ and CD8+ T cell vaccine responses in 27 HD patients and 26 low-risk control individuals (CI). The first two doses elicit weaker B cell and CD8+ T cell responses in HD than in CI, while CD4+ T cell responses are quantitatively similar. In HD, a third dose robustly boosts B cell responses, leads to convergent CD8+ T cell responses and enhances comparatively more Thelper (TH) immunity. Unsupervised clustering of single-cell features reveals phenotypic and functional shifts over time and between cohorts. The third dose attenuates some features of TH cells in HD (TNF/IL-2 skewing), while others (CCR6, CXCR6, PD-1 and HLA-DR overexpression) persist. Therefore, a third vaccine dose is critical to achieve robust multifaceted immunity in hemodialysis patients, although some distinct TH characteristics endure.
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BACKGROUND: Oculomotor nerve palsy (OMNP) is a known risk in surgical management of intracranial aneurysms. The aim of this study was to determine the risk factors for surgery-induced OMNP. METHODS: This retrospective study examined 585 patients with posterior communicating artery aneurysms treated surgically between January 2000 and July 2019. The patients were categorized into 2 groups according to whether they experienced OMNP. Multiple factors, including sex, age, history of subarachnoid hemorrhage, Hunt and Hess grade, Fisher grade, preoperative time, sizes, sides, number, orientation, intraoperative rupture, and morphology, were analyzed to identify factors associated with surgery-induced OMNP. RESULTS: The overall OMNP rate was 4.4%. In univariate analysis, large size (P < 0.001), posterior infratentorial projection (P = 0.003), number of subarachnoid hemorrhages (P = 0.005), and late preoperative time (P < 0.001) were associated with increased risk of OMNP. Overall, multivariate logistic regression analysis showed that size (10.1-25 mm: odds ratio [OR] 30.083, P = 0.001, 95% confidence interval [CI], 3.703-244.419; >25 mm: OR 62.179, P = 0.012, 95% CI, 2.402-1609.418), intraoperative rupture (OR 3.018, P = 0.035, 95% CI, 1.083-8.412), and preoperative time (>14 days: OR 10.985, P < 0.001, 95% CI, 3.840-31.428) were independent risk factors of surgery-induced OMNP. CONCLUSIONS: This study showed that size, intraoperative rupture, and preoperative time were independent predictors of surgery-induced OMNP. Use of advanced technologies during the operation can assist in avoiding this complication.
Subject(s)
Intracranial Aneurysm , Oculomotor Nerve Diseases , Subarachnoid Hemorrhage , Humans , Retrospective Studies , Intracranial Aneurysm/complications , Intracranial Aneurysm/surgery , Oculomotor Nerve Diseases/epidemiology , Oculomotor Nerve Diseases/etiology , Oculomotor Nerve Diseases/surgery , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/surgery , Risk Factors , Treatment OutcomeABSTRACT
Several SARS-CoV-2 Omicron subvariants have recently emerged, becoming the dominant circulating strains in many countries. These variants contain a large number of mutations in their Spike glycoprotein, raising concerns about vaccine efficacy. In this study, we evaluate the ability of plasma from a cohort of individuals that received three doses of mRNA vaccine to recognize and neutralize these Omicron subvariant Spikes. We observed that BA.4/5 and BQ.1.1 Spikes are markedly less recognized and neutralized compared to the D614G and the other Omicron subvariant Spikes tested. Also, individuals who have been infected before or after vaccination present better humoral responses than SARS-CoV-2 naive vaccinated individuals, thus indicating that hybrid immunity generates better humoral responses against these subvariants.
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Disentangling the relative contributions of deterministic and stochastic processes was critical to compressive understanding of underlying mechanism governing geographic pattern and assembly of phytoplankton community, while it was seldom performed in connected lakes under human pressure. Here, we investigated phytoplankton community pattern in relation to environmental and spatial factors over 81 lakes located in the middle and lower reaches of Yangtze River (MLYR) floodplain, where many lakes suffered from eutrophication and cyanobacterial blooms. A majority of MLYR lakes had higher phytoplankton abundance surpassing 107 cells/L and were dominated by common bloom-forming cyanobacterial genera, including Pseudanabaena, Microcystis, Merismopedia, Dolichospermum, Limnothrix, and Raphidiopsis. Phytoplankton community exhibited a striking geographical pattern both for taxonomic and functional compositions, while functional groups were less sensitive, and dissimilarity in communities displayed no significant increases with increasing geographical distance. Further, species richness explained much higher percentage of community variations than species turnover, indicating a reduced effect of environmental filtering of phytoplankton species with tolerance to similar environments in connected MLYR lakes. Both deterministic and stochastic processes governed assembly and biogeographic of phytoplankton community. Variation partition analysis showed that spatial factors exhibited greater influence on phytoplankton community compared to environmental variables. The stronger influence of spatial factors was further demonstrated by Mantel test and neutral community model. These findings indicate that deterministic and stochastic processes exhibited similar biogeographic patterns for phytoplankton community in MLYR lakes, but stochastic process was overwhelmingly dominated. Moreover, a large proportion of unexplained variation implies that complex interactions exist to shape assembly mechanism of phytoplankton community in MLYR lakes.
Subject(s)
Cyanobacteria , Phytoplankton , Humans , Lakes/microbiology , Rivers/microbiology , Eutrophication , ChinaABSTRACT
Neutralizing antibodies (NAbs) hold great promise for clinical interventions against SARS-CoV- 2 variants of concern (VOCs). Understanding NAb epitope-dependent antiviral mechanisms is crucial for developing vaccines and therapeutics against VOCs. Here we characterized two potent NAbs, EH3 and EH8, isolated from an unvaccinated pediatric patient with exceptional plasma neutralization activity. EH3 and EH8 cross-neutralize the early VOCs and mediate strong Fc-dependent effector activity in vitro. Structural analyses of EH3 and EH8 in complex with the receptor-binding domain (RBD) revealed the molecular determinants of the epitope-driven protection and VOC-evasion. While EH3 represents the prevalent IGHV3-53 NAb whose epitope substantially overlaps with the ACE2 binding site, EH8 recognizes a narrow epitope exposed in both RBD-up and RBD-down conformations. When tested in vivo, a single-dose prophylactic administration of EH3 fully protected stringent K18-hACE2 mice from lethal challenge with Delta VOC. Our study demonstrates that protective NAbs responses converge in pediatric and adult SARS-CoV-2 patients.
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While SARS-CoV-2 mRNA vaccination has been shown to be safe and effective in the general population, immunocompromised solid organ transplant recipients (SOTR) were reported to have impaired immune responses after one or two doses of vaccine. In this study, we examined humoral responses induced after the second and the third dose of mRNA vaccine in different SOTR (kidney, liver, lung and heart). Compared to a cohort of SARS-CoV-2 naive immunocompetent health care workers (HCW), the second dose induced weak humoral responses in SOTR, except for the liver recipients. The third dose boosted these responses but they did not reach the same level as in HCW. Interestingly, while the neutralizing activity against Delta and Omicron variants remained very low after the third dose, Fc-mediated effector functions in SOTR reached similar levels as in the HCW cohort. Whether these responses will suffice to protect SOTR from severe outcome remains to be determined.
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Due to the recrudescence of SARS-CoV-2 infections worldwide, mainly caused by Omicron BA.1 and BA.2 variants of concern, several jurisdictions are administering a mRNA vaccine boost. Here, we analyzed humoral responses induced after the second and third doses of mRNA vaccine in naive and previously-infected donors who received their second dose with an extended 16-week interval. We observed that the extended interval elicited robust humoral responses against VOCs, but this response was significantly diminished 4 months after the second dose. Administering a boost to these individuals brought back the humoral responses to the same levels obtained after the extended second dose. Interestingly, we observed that administering a boost to individuals that initially received a short 3-4 weeks regimen elicited humoral responses similar to those elicited in the long interval regimen. Nevertheless, humoral responses elicited by the boost in naive individuals did not reach those present in previously-infected vaccinated individuals.
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SARS-CoV-2 infection of host cells starts by binding of the Spike glycoprotein (S) to the ACE2 receptor. The S-ACE2 interaction is a potential target for therapies against COVID-19 as demonstrated by the development of immunotherapies blocking this interaction. Here, we present the commercially available VE607, comprised of three stereoisomers, that was originally described as an inhibitor of SARS-CoV-1. We show that VE607 specifically inhibits infection of SARS-CoV-1 and SARS-CoV-2 S-expressing pseudoviral particles as well as authentic SARS-CoV-2. VE607 stabilizes the receptor binding domain (RBD) in its "up" conformation. In silico docking and mutational analysis map the VE607 binding site at the RBD-ACE2 interface. The IC50 values are in the low micromolar range for pseudoparticles derived from SARS-CoV-2 Wuhan/D614G as well as from variants of concern (Alpha, Beta, Gamma, Delta and Omicron), suggesting that VE607 has potential for the development of drugs against SARS-CoV-2 infections.
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BACKGROUND: The reported incidence of sexually transmitted infections (STIs) in China has been increasing over the last decades, especially among drug users, which has become one of the main burdens of public health in China. This study was conducted to estimate the prevalence and associated factors of STIs among non-injecting methamphetamine (MA) users in Eastern China. METHODS: A cross-sectional survey was conducted among 632 MA users in Eastern China in 2017. Demographic characteristics, sexual behaviors, behaviors of MA use and sexual health knowledge were collected through questionnaire. First pass urine specimens were collected and detected for deoxyribonucleic acid (DNA) of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) with Nucleic Acid Amplification Technology (NAAT), while blood specimens were collected and detected for antibodies of Human immunodeficiency virus (HIV), Herpes simplex virus type-2 (HSV-2), and syphilis with enzyme-linked immune sorbent assay (ELISA). RESULTS: Among the 632 MA users, 464 (73.42%) were males, 60.92% were < 35 years of age, 546 (86.39%) were Shandong residents. 317 (50.16%, 95% CI 46.26-54.06%) participants were tested positive for at least one kind of STIs, including 242 (38.29%, 95% CI 34.50-42.08%) for HSV-2, 107 (16.93%, 95% CI 14.01-19.85%) for active syphilis, 46 (7.28%, 95% CI 5.25-9.31%) for treated syphilis, 40 (6.33%, 95% CI 4.43-8.23%) for CT, 6 (0.95%, 95% CI 0.19-1.71%) for HIV, and 3 (0.47%, 95% CI 0.06-1.00%) for NG infection. 99 (15.66%, 95% CI 12.83-18.49%) participants were co-infected with two kinds of STIs, including 91 (14.40%, 95% CI 11.66-17.14%) participants were co-infected with HSV-2 and syphilis. 14 (2.22%, 95% CI 1.07-3.37%) participants were co-infected with three kinds of STIs, and 4 HIV positive participants were co-infected with both syphilis and HSV-2. In the multiple logistic regression analysis, the results showed that females (adjusted OR [AOR] = 7.30, 95% CI 4.34-12.30) and individuals ≥ 35 years of age (AOR = 2.97, 95% CI 2.04-4.32) were more likely to test positive for STIs among MA users, whereas participants who acquired sexual health knowledge primarily from the Internet (AOR = 0.57, 95% CI 0.40-0.82) and those whose regular partners did not use drugs (AOR = 0.59, 95% CI 0.37-0.94) were less likely. CONCLUSIONS: This study found that the prevalence of HSV-2 and syphilis are alarming high among non-injecting MA users in Shandong Province in Eastern China. The prevention and control intervention of STIs among MA users in Shandong were needed, especially on females and MA users ≥ 35 years of age.