Unveiling the role of GAS41 in cancer progression.

GAS41, a member of the human YEATS domain family, plays a pivotal role in human cancer development. It serves as a highly promising epigenetic reader, facilitating precise regulation of cell growth and development by recognizing essential histone modifications, including histone acetylation, benzoylation, succinylation, and crotonylation. Functional readouts of these histone modifications often coincide with cancer progression. In addition, GAS41 functions as a novel oncogene, participating in numerous signaling pathways. Here, we summarize the epigenetic functions of GAS41 and its role in the carcinoma progression. Moving forward, elucidating the downstream target oncogenes regulated by GAS41 and the developing small molecule inhibitors based on the distinctive YEATS recognition properties will be pivotal in advancing this research field.

Spinal infection caused by Coxiella burnetii.

BACKGROUND: Spinal infection caused by Coxiella burnetii is rare and difficult to diagnose. Here we reported a case of spinal infection from Coxiella burnetii detected by the metagenomic next-generation sequencing (mNGS). CASE PRESENTATION: A 66-year-old male farmer with no medical history reported severe sharp low back pain, numbness and lower limb weakness for three years. Magnetic resonance imaging (MRI) revealed bone destruction and spinal cord compression within L1 and L2. mNGS testing showed that the inspected specimen collected from spinal lesion was detected positively for Coxiella burnetii. After receiving the combined treatment of antibiotic therapy and surgical intervention, the patient recovered well, and the sagittal MRI showed that vertebral edema signals disappeared and the graft of bone fused 16 months after surgery. CONCLUSION: The mNGS may be benefit for early diagnosis and intervention of non-specific spinal infection, and future studies should validate its effectiveness for clinical use in spinal infections. Additionally, antibiotic therapy combined with surgical intervention plays an important role on the treatment of spinal infection caused by Coxiella burnetii.

Exosomes-derived miR-548am-5p promotes colorectal cancer progression.

Exosomes are vital modulators in intercellular communication and microRNAs (miRNAs) are enriched within exosomes. MiRNAs are important participants in affecting colorectal cancer (CRC) progression, but the influence and latent mechanism of cancer-secreted exosomal miRNAs in colorectal cancer are not fully understood. miR-548am-5p has been reported to be differentially expressed in colon cancer and is indicated as a biomarker for colon cancer diagnosis at the early stage. In this study, we aimed to explore the role of exosomes-derived miR-548am-5p in CRC development. ISH and FISH were implemented to assess miR-548am-5p expression and location in CRC. CRC cells-secreted exosomes were identified via transmission electron microscopy and western blot. Colony formation, sphere formation and flow cytometry assessed the changes in proliferation, stemness and apoptosis of CRC cells. Bioinformatic analyses and mechanical experiments verified the binding of miR-548am-5p and RAR-related orphan receptor A (RORA). Our study identified miR-548am-5p was highly expressed in CRC tissues and cells. Tumor-derived exosomes expedited CRC cell proliferation and stemness along with secreted miR-548am-5p. Moreover, miR-548am-5p inhibition suppressed CRC cell proliferation and stemness while promoting cell apoptosis. RORA was the target mRNA of miR-548am-5p. Down-regulation of RORA was discovered in CRC and its expression was repressed by CRC cell-derived exosomes. As a result, our work elucidated that tumor-derived exosomal miR-548am-5p promoted CRC cell proliferation and stemness via targeting RORA, providing a valuable sight for CRC therapy.

The epidemiology of varicella and effectiveness of varicella vaccine in Ganyu, China: a long-term community surveillance study.

BACKGROUND: The real-world data of long-term protection under moderate vaccination coverage is limited. This study aimed to evaluate varicella epidemiology and the long-term effectiveness under moderate coverage levels in Ganyu District, Lianyungang City, Jiangsu Province. METHODS: This was a population-based, retrospective birth cohort study based on the immunization information system (IIS) and the National Notifiable Disease Surveillance System (NNDSS) in Ganyu District. Varicella cases reported from 2009 to 2020 were included to describe the epidemiology of varicella, and eleven-year consecutive birth cohorts (2008-2018) were included to estimate the vaccine effectiveness (VE) of varicella by Cox regression analysis. RESULTS: A total of 155,232 native children and 3,251 varicella cases were included. The vaccination coverage was moderate with 37.1%, correspondingly, the annual incidence of varicella infection increased 4.4-fold from 2009 to 2020. A shift of the varicella cases to older age groups was observed, with the peak proportion of cases shifting from 5-6 year-old to 7-8 year-old. The adjusted effectiveness of one dose of vaccine waned over time, and the adjusted VE decreased from 72.9% to 41.8% in the one-dose group. CONCLUSIONS: The insufficient vaccination coverage (37.1%) may have contributed in part to the rising annual incidence of varicella infection, and a shift of varicella cases to older age groups occurred. The effectiveness of one dose of varicella vaccine was moderate and waned over time. It is urgent to increase varicella vaccine coverage to 80% to reduce the incidence of varicella and prevent any potential shift in the age at infection in China.

Trace elements apportionment in forage, soil, and livestock in rangeland ecosystems along climatic gradients.

BACKGROUND: Alpine meadows, typical steppes, and deserts are among the globally important rangeland types that are generally distributed along temperature and precipitation gradients. Mineral losses caused by grazing are one of the key factors that can lead to instability or even degradation of these rangeland ecosystems. METHODS: We examined the concentrations of Cu, Fe, Mn, and Zn in soil, forage, and livestock dungs from diverse rangeland types in northwest China, to determine the relationships between these trace elements (TEs) concentrations and climatic factors (i.e., temperature, precipitation, and humidity), and to evaluate the potential risks of TEs deficiencies or excesses in these rangeland ecosystems. RESULTS: Forage Zn concentrations in forage of all three types of rangeland, and Cu concentrations in forage of the alpine meadow did not meet the growth requirements of grazing livestock. Concentrations of Cu, Fe, and Mn in forage and Fe, Mn, and Zn in livestock dungs had quadratic parabola relationships with temperature, precipitation, and humidity, but the relationships between climate factors and Cu, Fe, and Mn concentrations in soil were not significant. In addition, the abilities of the plant to absorb Cu, Fe, and Zn from soil were stronger in the typical steppe than that in the alpine meadows and desert. Also, the abilities of livestock to return TEs to soil were stronger in the alpine meadow than that in the typical steppe and desert. CONCLUSION: We derived a conceptual mode that the ratio of TE concentrations of the plant to soil and of livestock dung to forage represents the abilities of plants to absorb TEs from the soil matrix and livestock to return TEs to soil or to absorb TEs from forage, respectively. Results indicate potentially more serious risks of TEs deficiencies, especially that of Zn than previously considered in typical steppes and desert rangelands.

Synthesis of flavour-related linalool is regulated by PpbHLH1 and associated with changes in DNA methylation during peach fruit ripening.

Linalool is one of the common flavour-related volatiles across the plant kingdom and plays an essential role in determining consumer liking of plant foods. Although great process has been made in identifying terpene synthase (TPS) genes associated with linalool synthesis, much less is known about regulation of this pathway. We initiated study by identifying PpTPS3 encoding protein catalysing enantiomer (S)-(+)-linalool synthesis, which is a major linalool component (˜70%) observed in ripe peach fruit. Overexpression of PpTPS3 led to linalool accumulation, while virus-induced gene silencing of PpTPS3 led to a 66.5% reduction in linalool content in peach fruit. We next identified transcription factor (TF) PpbHLH1 directly binds to E-box (CACATG) in the PpTPS3 promoter and activates its expression based on yeast one-hybrid assay and EMSA analysis. Significantly positive correlation was also observed between PpbHLH1 expression and linalool production across peach cultivars. Peach fruit accumulated more linalool after overexpressing PpbHLH1 in peach fruit and reduced approximately 54.4% linalool production after silencing this TF. DNA methylation analysis showed increased PpTPS3 expression was associated with decreased 5 mC level in its promoter during peach fruit ripening, but no reverse pattern was observed for PpbHLH1. Arabidopsis and tomato fruits transgenic for peach PpbHLH1 synthesize and accumulate higher levels of linalool compared with wild-type controls. Taken together, these results would greatly facilitate efforts to enhance linalool production and thus improve flavour of fruits.

A novel risk score model based on eight genes and a nomogram for predicting overall survival of patients with osteosarcoma.

BACKGROUND: This study aims to identify a predictive model to predict survival outcomes of osteosarcoma (OS) patients. METHODS: A RNA sequencing dataset (the training set) and a microarray dataset (the validation set) were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, respectively. Differentially expressed genes (DEGs) between metastatic and non-metastatic OS samples were identified in training set. Prognosis-related DEGs were screened and optimized by support vector machine (SVM) recursive feature elimination. A SVM classifier was built to classify metastatic and non-metastatic OS samples. Independent prognosic genes were extracted by multivariate regression analysis to build a risk score model followed by performance evaluation in two datasets by Kaplan-Meier (KM) analysis. Independent clinical prognostic indicators were identified followed by nomogram analysis. Finally, functional analyses of survival-related genes were conducted. RESULT: Totally, 345 DEGs and 45 prognosis-related genes were screened. A SVM classifier could distinguish metastatic and non-metastatic OS samples. An eight-gene signature was an independent prognostic marker and used for constructing a risk score model. The risk score model could separate OS samples into high and low risk groups in two datasets (training set: log-rank p < 0.01, C-index = 0.805; validation set: log-rank p < 0.01, C-index = 0.797). Tumor metastasis and RS model status were independent prognostic factors and nomogram model exhibited accurate survival prediction for OS. Additionally, functional analyses of survival-related genes indicated they were closely associated with immune responses and cytokine-cytokine receptor interaction pathway. CONCLUSION: An eight-gene predictive model and nomogram were developed to predict OS prognosis.

Ginsenoside Rb1 protects against spinal cord ischemia-reperfusion injury in rats by downregulating the Bax/Bcl-2 ratio and caspase-3 and p-Ask-1 levels.

The aim of this study was to confirm the effects of ginsenoside Rb1 on neural cell apoptosis in the spinal cord of rats with spinal cord ischemia-reperfusion injury (SCII) and to explore its potential mechanisms. A total of 100 healthy adult Sprague-Dawley (SD) rats were randomly divided into four groups: normal control (n = 10), sham-operated (n = 10), SCII model (n = 40), and ginsenoside Rb1-treated groups (n = 40). Basso, Beattie, Bresnahan (BBB) scale was used to examine rat hindlimb locomotor function. Nissl and Tunnel staining were used to observe neural cell injury and apoptosis, respectively, in the spinal cord of rats with SCII. Immunofluorescence staining was performed to detect the expression of Bax and Bcl-2. The levels of caspase-3 and phosphorylated Ask-1 (p-Ask-1) were detected by western blotting. Ginsenoside Rb1 prevented neural cell apoptosis in the spinal cord and improved hindlimb locomotor dysfunction of rats (P < .05). Moreover, SCII-induced upregulation of caspase-3 and p-Ask-1 levels and the Bax/Bcl-2 ratio were significantly decreased by ginsenoside Rb1 (P < .05). The protective effects of ginsenoside Rb1 on neural cells in the spinal cord of rats with SCII were mediated by the ginsenoside Rb1-induced downregulation of caspase-3 and p-Ask-1 levels and the Bax/Bcl-2 ratio.

Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China.

BACKGROUND: Enterovirus 71 (EV71) is one of the major causative agents of outbreaks of hand, foot, and mouth disease or herpangina worldwide. This phase 3 trial was designed to evaluate the efficacy, safety, and immunogenicity of an EV71 vaccine. METHODS: We conducted a randomized, double-blind, placebo-controlled, multicenter trial in which 10,007 healthy infants and young children (6 to 35 months of age) were randomly assigned in a 1:1 ratio to receive two intramuscular doses of either EV71 vaccine or placebo, 28 days apart. The surveillance period was 12 months. The primary end point was the occurrence of EV71-associated hand, foot, and mouth disease or herpangina. RESULTS: During the 12-month surveillance period, EV71-associated disease was identified in 0.3% of vaccine recipients (13 of 5041 children) and 2.1% of placebo recipients (106 of 5028 children) in the intention-to-treat cohort. The vaccine efficacy against EV71-associated hand, foot, and mouth disease or herpangina was 94.8% (95% confidence interval [CI], 87.2 to 97.9; P<0.001) in this cohort. Vaccine efficacies against EV71-associated hospitalization (0 cases vs. 24 cases) and hand, foot, and mouth disease with neurologic complications (0 cases vs. 8 cases) were both 100% (95% CI, 83.7 to 100 and 42.6 to 100, respectively). Serious adverse events occurred in 111 of 5044 children in the vaccine group (2.2%) and 131 of 5033 children in the placebo group (2.6%). In the immunogenicity subgroup (1291 children), an anti-EV71 immune response was elicited by the two-dose vaccine series in 98.8% of participants at day 56. An anti-EV71 neutralizing antibody titer of 1:16 was associated with protection against EV71-associated hand, foot, and mouth disease or herpangina. CONCLUSIONS: The EV71 vaccine provided protection against EV71-associated hand, foot, and mouth disease or herpangina in infants and young children. (Funded by Sinovac Biotech; ClinicalTrials.gov number, NCT01507857.).

[Histocompatibility of nano-hydroxyapatite/poly-co-glycolic acid tissue engineering bone modified by mesenchymal stem cells with vascular endothelial frowth factor].

OBJECTIVE: To explorec Histocompatibility of nano-hydroxyapatite/poly-co-glycolic acid tissue engineering bone modified by mesenchymal stem cells with vascular endothelial frowth factor transinfected. METHODS: Rat bone marrow mesenchymal stem cells (BMSCs) was separated, using BMSCs as target cells, and then vascular endothelial growth factor (VEGF) gene was transfected. Composite bone marrow mesenchymal stem cells and cells transfected with nano-hydroxyapatite (HA)/polylactic-co-glycolic acid (PLGA). The composition of cell and scaffold was observed. RESULTS: The blank plasmid transfection was 39.1%, 40.1% in VEGF group. The cell adhesion and growth was found on the scaffold pore wall after 5 days, and the number of adherent cells in the nano-HA/PLGA composite scaffold material basically had no significant difference in both. CONCLUSION: Although the nano-HA/PLGA scaffold material is still not fully meet the requirements of the matrix material for bone tissue engineering, but good biocompatibility, structure is its rich microporous satisfaction in material mechanics, toughening, enhanced obviously. Composition scaffold with BMSCs transfected by VEGF plasmid, the ability of angiogenesis is promoted.

Highly sensitive force sensor based on optical microfiber asymmetrical Fabry-Perot interferometer.

An asymmetrical Fabry-Perot interferometric (AFPI) force sensor is fabricated based on a narrowband reflection of low-reflectivity fiber Bragg grating (LR-FBG) and a broadband Fresnel reflection of the cleaved fiber end. The AFPI sensor includes a section of microfiber made by tapering and it achieves a force sensitivity of 0.221 pm/µN with a tapered microfiber of 40 mm length and 6.1 µm waist diameter. Compared with similar AFPI structure in 125 µm-diameter single mode fiber, the force sensitivity of the microfiber AFPI structure is greatly enhanced due to its smaller diameter and can be optimized for different force scales by controlling the diameter. The fabrication process of the AFPI sensor is simple and cost-effective. The AFPI sensor has better multiplexing capacity than conventional extrinsic fiber-optic Fabry-Perot sensors, while it also release the requirement on the wavelength matching of the FBG-pair-based FPI.

[Effects of Xiaoyao Powder Extract in co-culture model of melanoma cells and keratinocytes on expression of tyrosinase and its related protein].

OBJECTIVE: To observe the effects and mechanism of Xiaoyao Powder extract on the content of melanin in co-culture model of melanoma cells and keratinocytes. METHODS: Eluting components of Xiaoyao Powder was collected by AB-8 macroporous resin column. Different concentration extracts of Xiaoyao Powder were added into the co-culture model of A375 melanoma cells and HaCat ke- ratinocytes. Hunt method was used to detected the content of melanin. RT-PCR assay was used to detect the effects of the extract of Xi- aoyao Powder on the TYR,TRP-1 and TRP-2 mRNA expression in A375 melanoma cells. RESULTS: Compared with the control group,the extract of Xiaoyao Powder down-regulated content of melanin and mRNA expression of TYR,TRP-1 and TRP-2 in A375 melanoma cells by 82.23% ,93. 01% and 29. 11% ,23.78% ,20. 05% ;25. 13% ,15.02% ,11.64% ,respectively(P < 0. 01). CONCLUSION: The extract of Xiaoyao Powder can decrease the melanogenesis by down-regulating the mRNA expression of tyrosinase and its related protein.

Identifying Relationships between Glutathione S-Transferase-2 Single Nucleotide Polymorphisms and Hypoxia Tolerance and Growth Traits in Macrobrachium nipponense.

Investigating hypoxia tolerance and growth trait single nucleotide polymorphisms (SNPs) in Macrobrachium nipponense is conducive to cultivating prawns with hypoxia tolerance and good growth characteristics. The glutathione S-transferase-2 gene (GST-2) has been shown to regulate hypoxia responses in M. nipponense. In this study, we identified a single GST-2 SNP in M. nipponense, and analyzed its regulatory relationship with hypoxia tolerance and growth. The GST-2 sequence was amplified with a polymerase chain reaction from 197 "Taihu Lake No. 3", "Taihu Lake No. 2", and Pearl River population samples to identify SNP loci. The full-length Mn-GST2 sequence was 2317 bp, including three exons and two introns. In total, 38 candidate SNP loci were identified from GST-2 using Mega11.0 comparisons, with most loci moderately polymorphic in terms of genetic diversity. Locus genotypes were also analyzed, and basic genetic parameters for loci were calculated using Popgene32 and PIC_CALC. The expected heterozygosity of the 38 SNP loci ranged from 0.2334 to 0.4997, with an average of 0.4107, while observed heterozygosity ranged from 0.1929 to 0.4721, with an average of 0.3401. The polymorphic information content ranged from 0.21 to 0.37. From SPSS analyses, the G+256A locus was significantly correlated with hypoxia tolerance across all three M. nipponense populations, while the SNP loci A+261C, C+898T, A+1370C, and G+1373T were significantly associated with growth traits. Further analyses revealed that the T+2017C locus was significantly correlated with hypoxia tolerance in "Taihu Lake No. 2" populations, G+256A, A+808T, C+1032T, and A+1530G loci were significantly correlated with hypoxia tolerance in "Taihu Lake No. 3" populations, while no SNP loci were correlated with hypoxia tolerance in Pearl River populations. A+1370C and G+1373T loci, which were associated with growth traits, exhibited a high degree of linkage disequilibrium (r2 = 0.89 and r2 > 0.8), suggesting potential genetic linkage. Our data suggest associations between hypoxia tolerance and growth trait SNP loci in M. nipponense, and provide valuable evidence for the genetic improvement of growth and hypoxia tolerance in this prawn species.

Single-cell disulfidptosis regulator patterns guide intercellular communication of tumor microenvironment that contribute to kidney renal clear cell carcinoma progression and immunotherapy.

Background: Disulfidptosis, an emerging type of programmed cell death, plays a pivotal role in various cancer types, notably impacting the progression of kidney renal clear cell carcinoma (KIRC) through the tumor microenvironment (TME). However, the specific involvement of disulfidptosis within the TME remains elusive. Methods: Analyzing 41,784 single cells obtained from seven samples of KIRC through single-cell RNA sequencing (scRNA-seq), this study employed nonnegative matrix factorization (NMF) to assess 24 disulfidptosis regulators. Pseudotime analysis, intercellular communication mapping, determination of transcription factor activities (TFs), and metabolic profiling of the TME subgroup in KIRC were conducted using Monocle, CellChat, SCENIC, and scMetabolism. Additionally, public cohorts were utilized to predict prognosis and immune responses within the TME subgroup of KIRC. Results: Through NMF clustering and differential expression marker genes, fibroblasts, macrophages, monocytes, T cells, and B cells were categorized into four to six distinct subgroups. Furthermore, this investigation revealed the correlation between disulfidptosis regulatory factors and the biological traits, as well as the pseudotime trajectories of TME subgroups. Notably, disulfidptosis-mediated TME subgroups (DSTN+CD4T-C1 and FLNA+CD4T-C2) demonstrated significant prognostic value and immune responses in patients with KIRC. Multiple immunohistochemistry (mIHC) assays identified marker expression within both cell clusters. Moreover, CellChat analysis unveiled diverse and extensive interactions between disulfidptosis-mediated TME subgroups and tumor epithelial cells, highlighting the TNFSF12-TNFRSF12A ligand-receptor pair as mediators between DSTN+CD4T-C1, FLNA+CD4T-C2, and epithelial cells. Conclusion: Our study sheds light on the role of disulfidptosis-mediated intercellular communication in regulating the biological characteristics of the TME. These findings offer valuable insights for patients with KIRC, potentially guiding personalized immunotherapy approaches.

Immunogenicity and safety of an ORF7-deficient skin-attenuated and neuro-attenuated live vaccine for varicella: a randomised, double-blind, controlled, phase 2a trial.

BACKGROUND: The Oka varicella vaccine strain remains neurovirulent and can establish lifelong latent infection, raising safety concerns about vaccine-related herpes zoster. In this study, we aimed to evaluate the immunogenicity and safety of a skin-attenuated and neuro-attenuated varicella vaccine candidate (v7D vaccine). METHODS: We did this randomised, double-blind, controlled, phase 2a clinical trial in Jiangsu, China. Healthy children aged 3-12 years with no history of varicella infection or vaccination were enrolled and randomly assigned (1:1:1:1) to receive a single subcutaneous injection of the v7D vaccine at 3·3 log10 plaque forming units (PFU; low-dose v7D group), 3·9 log10 PFU (medium-dose v7D group), and 4·2 log10 PFU (high-dose v7D group), or the positive control varicella vaccine (vOka vaccine group). All the participants, laboratory personnel, and investigators other than the vaccine preparation and management staff were masked to the vaccine allocation. The primary outcome was assessment of the geometric mean titres (GMTs) and seroconversion rates of anti-varicella zoster virus immunoglobulin G (IgG) induced by different dose groups of v7D vaccine at 0, 42, 60, and 90 days after vaccination in the per-protocol set for humoral immune response analysis. Safety was a secondary outcome, focusing on adverse events within 42 days post-vaccination, and serious adverse events within 6 months after vaccination. This study was registered on Chinese Clinical Trial Registry, ChiCTR2000034434. FINDINGS: On Aug 18-21, 2020, 842 eligible volunteers were enrolled and randomly assigned treatment. After three participants withdrew, 839 received a low dose (n=211), middle dose (n=210), or high dose (n=210) of v7D vaccine, or the vOka vaccine (n=208). In the per-protocol set for humoral immune response analysis, the anti-varicella zoster virus IgG antibody response was highest at day 90. At day 90, the seroconversion rates of the low-dose, medium-dose, and high-dose groups of v7D vaccine and the positive control vOka vaccine group were 100·0% (95% CI 95·8-100·0; 87 of 87 participants), 98·9% (93·8-100·0; 87 of 88 participants), 97·8% (92·4-99·7; 91 of 93 participants), and 96·4% (89·8-99·2; 80 of 83 participants), respectively; the GMTs corresponded to values of 30·8 (95% CI 26·2-36·0), 31·3 (26·7-36·6), 28·2 (23·9-33·2), and 38·5 (31·7-46·7). The v7D vaccine, at low dose and medium dose, elicited a humoral immune response similar to that of the vOka vaccine. However, the high-dose v7D vaccine induced a marginally lower GMT compared with the vOka vaccine at day 90 (p=0·027). In the per-protocol set, the three dose groups of the v7D vaccine induced a similar humoral immune response at each timepoint, with no statistically significant differences. The incidence of adverse reactions in the low-dose, medium-dose, and high-dose groups of v7D vaccine was significantly lower than that in the vOka vaccine group (17% [35 of 211 participants], 20% [41 of 210 participants], and 13% [27 of 210 participants] vs 24% [50 of 208 participants], respectively; p=0·025), especially local adverse reactions (10% [22 of 211 participants], 14% [30 of 210 participants] and 9% [18 of 210 participants] vs 18% [38 of 208 participants], respectively; p=0·016). None of the serious adverse events were vaccine related. INTERPRETATION: The three dose groups of the candidate v7D vaccine exhibit similar humoral immunogenicity to the vOka vaccine and are well tolerated. These findings encourage further investigations on two-dose vaccination schedules, efficacy, and the potential safety benefit of v7D vaccine in the future. FUNDING: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, the Fundamental Research Funds for the Central Universities, and Beijing Wantai. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Head-to-head immunogenicity comparison of an Escherichia coli-produced 9-valent human papillomavirus vaccine and Gardasil 9 in women aged 18-26 years in China: a randomised blinded clinical trial.

BACKGROUND: An Escherichia coli-produced human papillomavirus (HPV) 16 and 18 bivalent vaccine (Cecolin) was prequalified by WHO in 2021. This study aimed to compare the immunogenicity of the E coli-produced HPV 9-valent vaccine Cecolin 9 (against HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) with Gardasil 9. METHODS: This was a randomised, single-blind trial conducted in China. Healthy non-pregnant women aged 18-26 years, who were not breastfeeding and with no HPV vaccination history, were enrolled in the Ganyu Centre for Disease Control and Prevention (Lianyungang City, Jiangsu Province, China). Women were stratified by age (18-22 years and 23-26 years) and randomly assigned (1:1) using a permutated block size of eight to receive three doses of Cecolin 9 or Gardasil 9 at day 0, day 45, and month 6. All participants, as well as study personnel without access to the vaccines, were masked. Neutralising antibodies were measured by a triple-colour pseudovirion-based neutralisation assay. The primary outcomes, seroconversion rates and geometric mean concentrations (GMCs) at month 7, were analysed in the per-protocol set for immunogenicity (PPS-I). Non-inferiority was identified for the lower limit of the 95% CI of the GMC ratio (Cecolin 9 vs Gardasil 9) at a margin of 0·5 and a seroconversion rate difference (Cecolin 9-Gardasil 9) at a margin of -5%. This study was registered at ClinicalTrials.gov (NCT04782895) and is completed. FINDINGS: From March 14 to 18, 2021, a total of 553 potential participants were screened, of which 244 received at least one dose of Cecolin 9 and 243 received at least one dose of Gardasil 9. The seroconversion rates for all HPV types in both groups were 100% in the PPS-I, with the values of the lower limits of 95% CIs for seroconversion rate differences ranging between -1·8% and -1·7%. The GMC ratios of five types were higher than 1·0, with the highest ratio, for HPV 58, at 1·65 (95% CI 1·38-1·97), and those of four types were lower than 1·0, with the lowest ratio, for HPV 11, at 0·79 (0·68-0·93). The incidence of adverse reactions in both groups was similar (43% [104/244] vs 47% [115/243]). INTERPRETATION: Cecolin 9 induced non-inferior HPV type-specific immune responses compared with Gardasil 9 and is a potential candidate to accelerate the elimination of cervical cancer by allowing for global accessibility to 9-valent HPV vaccinations, especially in low-income and middle-income countries. FUNDING: National Natural Science Foundation, Fujian Provincial Natural Science Foundation, Xiamen Science and Technology Plan Project, Fundamental Research Funds for the Central Universities, CAMS Innovation Fund for Medical Sciences of China, and Xiamen Innovax.

Seroepidemiology of human enterovirus71 and coxsackievirusA16 in Jiangsu province, China.

BACKGROUND: The major etiology of hand, foot and mouth disease (HFMD) is infection with human enterovirus A (HEV-A). Among subtypes of HEV-A, coxsackievirusA16 (CoxA16) and enterovirus 71 (EV71) are major causes for recurrent HFMD among infants and children in Jiangsu Province, mainland China. Here, we analyzed maternal antibodies between prenatal women and their neonates, to determine age-specific seroprevalence of human EV71 and CoxA16 infections in infants and children aged 0 to 15 years. The results may facilitate the development of immunization against HFMD. METHODS: This study used cross-section of 40 pairs of pregnant women and neonates and 800 subjects aged 1 month to 15 years old. Micro-dose cytopathogenic effects measured neutralizing antibodies against EV71 and CoxA16. Chi-square test compared seroprevalence rates between age groups and McNemar test, paired-Samples t-test and independent-samples t-test analyzed differences of geometric mean titers. RESULTS: A strong correlation between titers of neutralizing antibody against EV71 and CoxA16 in prenatal women and neonates was observed (rEV71 = 0.67, rCoxA16 = 0.56, respectively, p < 0.05). Seroprevalence rates of anti-EV71 antibody gradually decreased with age between 0 to 6 months old, remained low between 7 to 11 months (5.0-10.0%), and increased between 1 and 4 years (22.5-87.5%). Age-specific seroprevalence rates of anti-EV71 antibody stabilized in >80% of children between 5 to 15 years of age. However, seroprevalence rates of anti-CoxA16 antibody were very low (0.0-13.0%) between 0 to 6 months of age, gradually increased between 7 months to 4 years (15.0-70.0%), and stabilized at 54.0% (108/200) between 5 to 15 years. Seroprevalence rates against EV71 and CoxA16 were low under 1 year (0.0-10.0%), and showed an age dependent increase with high seroprevalence (52.5-62.5%) between 4 and 10 years of age. CONCLUSIONS: Concomitant infection of EV71 and CoxA16 was common in Jiangsu Province. Therefore, development of bivalent vaccine against both EV71 and CoxA16 is critical. The optimal schedule for vaccination may be 4 to11 months of age.

Expression of the Circadian Clock Gene ARNTL associated with DNA repair gene and prognosis of patient with osteosarcoma.

PURPOSE: The study objects were to explore the correlation between the biological role of clock genes and clinical indicators in patients with osteosarcoma (OS). METHODS: We acquired the clinical information and RNA sequencing data of OS samples from the TARGET database. The protein-protein interaction (PPI) network and expression correlation analysis of clock genes were performed. Then, the functional enrichment analysis of clock genes was analyzed. The survival analysis of clock genes in patients of OS was carried out by univariate cox regression, Kaplan-Meier (KM) curve and multivariate cox regression methods. Moreover, the spearmen correlation analysis was performed to explore the correlation between clock genes and DNA repair genes in patients with OS. RESULTS: The PPI network and expression correlation analysis of clock genes indicated that the clock genes were highly correlated with each other. The survival analysis of clock genes found that clock gene ARNTL is a protective factor for the prognosis of patients with OS. We found that ARNTL was positively related to DNA repair genes and was involved in the biological process of DNA damage repair in patients with OS. CONCLUSIONS: ARNTL may affect the prognosis and chemotherapy response of patients with OS by regulating DNA repair pathways.

Polymer nanotherapeutics to correct autoimmunity.

The immune system maintains homeostasis and protects the body from pathogens, mutated cells, and other harmful substances. When immune homeostasis is disrupted, excessive autoimmunity will lead to diseases. To inhibit the unexpected immune responses and reduce the impact of treatment on immunoprotective functions, polymer nanotherapeutics, such as nanomedicines, nanovaccines, and nanodecoys, were developed as part of an advanced strategy for precise immunomodulation. Nanomedicines transport cytotoxic drugs to target sites to reduce the occurrence of side effects and increase the stability and bioactivity of various immunomodulating agents, especially nucleic acids and cytokines. In addition, polymer nanomaterials carrying autoantigens used as nanovaccines can induce antigen-specific immune tolerance without interfering with protective immune responses. The precise immunomodulatory function of nanovaccines has broad prospects for the treatment of immune related-diseases. Besides, nanodecoys, which are designed to protect the body from various pathogenic substances by intravenous administration, are simple and relatively noninvasive treatments. Herein, we have discussed and predicted the application of polymer nanotherapeutics in the correction of autoimmunity, including treating autoimmune diseases, controlling hypersensitivity, and avoiding transplant rejection.

Co-N heteroatomic interface engineering in peanut Shell-Derived porous carbon for enhanced oxygen reduction reaction.

The development of high-efficiency and low-cost oxygen reduction electrocatalysts have become an urgent need to push fuel cells into practical application. Herein, an effective electrocatalyst Co/NC was successfully constructed, which was derived from abundant peanut shells, obtained by doping with cobalt ions and pyrolyzing in NH3 atmosphere. Due to the abundant Co-N active sites triggered by Co-N heteroatomic interface, the prepared electrocatalysts present excellent oxygen reduction reaction (ORR) performance with more positive half-wave potential (E1/2 = 0.83 V), incremental limiting current density (JL = 5.45 mA cm-2), higher durability and stronger resistance to methanol, which is superior to that of Pt/C (E1/2 = 0.81 V and JL = 5.19 mA cm-2). This work proposes a potential strategy to synthesize efficient ORR electrocatalysts to instead of Pt-based catalysts.