The impact of hypertension on clinical manifestations of Omicron variant BA.1 infection in adult patients.

COVID-19 caused by Omicron BA.1 has resulted in a global humanitarian crisis. In this COVID-19 pandemic era, hypertension has been receiving increased attention. Omicron BA.1 infection combined with hypertension created a serious public health problem and complicated the treatment and prognosis of COVID-19. The aim of our study was to assess the implications of hypertension for the clinical manifestations of adult patients (APs) infected with Omicron BA.1. This single-center retrospective cohort study enrolled consecutive COVID-19 APs, who were admitted to Tianjin First Central Hospital from 01 August 2022 to 30 November 2022. All included APs were divided into two groups: hypertension and non-hypertension group. The APs' baseline demographic, laboratory, clinical, and radiological characteristics were collected and analyzed. Of 512 APs admitted with PCR proven COVID-19, 161 (31.45%) APs had comorbid hypertension. Hypertension APs have older age, higher body mass index, lower Ct-values of the viral target genes at admission, and longer hospital stay than non-hypertension APs. Furthermore, hypertension aggravates the clinical classification, impairs liver, kidney, and myocardium function, and abnormalizes the coagulation system in Omicron BA.1- infected APs. Moreover, hypertension elevates inflammation levels and lung lesion involvement while weakened virus-specific IgM level in APs with Omicron BA.1 infection. Hypertension APs tend to have worse clinical conditions at baseline than those non-hypertension APs. This study indicates that hypertension is a contributor to the poor clinical manifestations of Omicron BA.1-infected APs and supports that steps to control blood pressure should be a vital consideration for reducing the burden of Omicron BA.1 infection in hypertension individuals. IMPORTANCE: This study provided inclusive insight regarding the relationship between hypertension and Omicron BA.1 infection and supported that hypertension was an adverse factor for COVID-19 APs. In conclusion, this study showed that hypertension was considered to be associated with severe conditions, and a contributor to poor clinical manifestations. Proper medical management of hypertension patients is an imperative step in mitigating the severity of Omicron BA.1 variant infection.

Cell communication pathway prognostic model identified detrimental neurodevelopmental pathways in neuroblastoma.

Neurodevelopmental cell communication plays a crucial role in neuroblastoma prognosis. However, determining the impact of these communication pathways on prognosis is challenging due to limited sample sizes and patchy clinical survival information of single cell RNA-seq data. To address this, we have developed the cell communication pathway prognostic model (CCPPM) in this study. CCPPM involves the identification of communication pathways through single-cell RNA-seq data, screening of prognosis-significant pathways using bulk RNA-seq data, conducting functional and attribute analysis of these pathways, and analyzing the post-effects of communication within these pathways. By employing the CCPPM, we have identified ten communication pathways significantly influencing neuroblastoma, all related to axongenesis and neural projection development, especially the BMP7-(BMPR1B-ACVR2B) communication pathway was found to promote tumor cell migration by activating the transcription factor SMAD1 and regulating UNK and MYCBP2. Notably, BMP7 expression was higher in neuroblastoma samples with distant metastases. In summary, CCPPM offers a novel approach to studying the influence of cell communication pathways on disease prognosis and identified detrimental communication pathways related to neurodevelopment.

TET3 gene rs828867 G>A polymorphism reduces neuroblastoma risk in Chinese children.

Objective: Neuroblastoma (NB) is a prevalent pediatric tumor originating from primordial neural crest cells. As one of the latest epigenetics investigations focuses, RNA 5-methylcytosine (m5C) is closely related to cancer risk. TET methylcytosine dioxygenase 3 (TET3) is a demethylase for m5C modification. Whether there is an association between TET3 gene polymorphisms and neuroblastoma risk remains unclear. Methods: We conducted an epidemiological study in 402 patients and 473 controls to evaluate the relationship between TET3 gene SNPs (rs7560668 T > C, rs828867 G > A, and rs6546891 A > G) and NB susceptibility. Results: Our results showed that rs828867 G > A significantly reduced NB risk in Chinese children [GA vs. GG, adjusted odds ratio (OR) = 0.72, 95% confidence interval (CI) = 0.52-0.98, P=0.040; GA/AA vs. GG, adjusted OR = 0.74, 95% CI = 0.55-0.998, P=0.048]. Individuals with 2-3 risk genotypes had a significantly higher NB risk than those with 0-1 risk genotypes (adjusted OR = 1.40, 95% CI = 1.04-1.88, P=0.027). The stratified analysis showed that the rs828867 G > A associated with decreased NB risk is remarkable among children aged >18 months (adjusted OR = 0.67, 95% CI = 0.46-0.96, P=0.029) and patients at clinical III + IV stages (adjusted OR = 0.67, 95% CI = 0.45-0.98, P=0.040). Compared with the 0-1 risk genotype, the concurrence of 2-3 risk genotypes significantly increased NB risk in the following subgroups: children aged >18 months and patients at clinical III + IV stages. GTEx analysis suggested that rs828867 G > A was significantly associated with RP11-287D1.4 and POLE4 mRNA expression. Conclusions: Overall, our results revealed that rs828867 G > A in the TET3 gene is significantly associated with predisposition to NB.

Genetic variants of m7G modification genes influence neuroblastoma susceptibility.

Objective: Neuroblastoma is a life-threatening pediatric solid tumor whose etiology remains unclear. N7-methylguanosine (m7G) is one of the most important epigenetic modifications of RNA, which plays a crucial role in tumorigenesis. The m7G-mediated genes METTL1 and WDR4 also have been reported to be dysregulated in various cancers. However, the implications of METTL1 and WDR4 in neuroblastoma have not been clarified. Methods: Given the oncogenic potential of m7G modification, we performed a case-control study to assess the association of METTL1 and WDR4 genes polymorphisms with neuroblastoma risk in a Chinese population consisting of 402 cases and 473 controls. Odds ratios (ORs) and 95 % confidence intervals (CIs) were applied to evaluate the associations between studied polymorphisms and neuroblastoma risk. The adjusted odds ratio (AOR) was adjusted for age and gender. Results: Overall, four polymorphisms were significantly associated with neuroblastoma risk, including METTL1 rs2291617 (recessive model: adjusted OR = 1.59, 95 % CI = 1.08-2.34, P = 0.019), WDR4 rs2156316 (dominant model: adjusted OR = 0.74, 95 % CI = 0.57-0.97, P = 0.028), WDR4 rs6586250 (dominant model: adjusted OR = 0.59, 95 % CI = 0.42-0.84, P = 0.004) and WDR4 rs15736 (dominant model: adjusted OR = 0.60, 95 % CI = 0.42-0.85, P = 0.004). Stratified analysis showed stronger correlations between significant polymorphisms and neuroblastoma risk among subgroups divided by age, gender, tumor origin, and clinical stage. Furthermore, expression quantitative trait loci (eQTL) analysis revealed that significant polymorphisms were associated with the expression of the adjacent genes. Conclusions: Our study indicated that four polymorphisms in m7G-mediated genes contribute to neuroblastoma susceptibility in the eastern Chinese population. However, our findings should be verified further by large-scale and well-designed studies.

Screening of novel biomarkers for acute kidney transplant rejection using DIA-MS based proteomics.

BACKGROUND: Kidney transplantation is the preferred treatment for patients with end-stage renal disease. However, acute rejection poses a threat to the graft long-term survival. The aim of this study was to identify novel biomarkers to detect acute kidney transplant rejection. METHODS: The serum proteomic profiling of kidney transplant patients with T cell-mediated acute rejection (TCMR) and stable allograft function (STA) was analyzed using data-independent acquisition mass spectrometry (DIA-MS). The differentially expressed proteins (DEPs) of interest were further verified by enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 131 DEPs were identified between STA and TCMR patients, 114 DEPs were identified between mild and severe TCMR patients. The verification results showed that remarkable higher concentrations of serum amyloid A protein 1 (SAA1) and insulin like growth factor binding protein 2 (IGFBP2), and lower fetuin-A (AHSG) concentration were found in TCMR patients when compared with STA patients. We also found higher SAA1 concentration in severe TCMR group when compared with mild TCMR group. The receiver operating characteristics (ROC) analysis further confirmed that combination of SAA1, AHSG, and IGFBP2 had excellent performance in the acute rejection diagnosis. CONCLUSIONS: Our data demonstrated that serum SAA1, AHSG, and IGFBP2 could be effective biomarkers for diagnosing acute rejection after kidney transplantation. DIA-MS has great potential in biomarker screening of kidney transplantation.

ALKBH1 rs2267755 C>T polymorphism decreases neuroblastoma risk in Chinese children.

Neuroblastoma is a highly malignant extracranial solid tumor in pediatrics. ALKBH1 as a recently discovered DNA N6-methyldeoxyadenosine (6mA) demethylase closely links to tumorigenesis. Whether the ALKBH1 polymorphism contributes to neuroblastoma risk remains unclear. In the present study, we genotyped the ALKBH1 single nucleotide polymorphisms (SNPs) in 402 neuroblastoma patients and 473 healthy controls by TaqMan assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were also calculated to evaluate the strength of the association. Our result exhibited that the rs2267755 C>T (CT vs. CC, adjusted OR=0.69, 95% CI=0.50-0.94, P=0.019) is significantly associated with reduced neuroblastoma risk. And its protective effect is particularly significant in children with tumors originating from the retroperitoneal. Combined genotype analysis revealed that carriers with 1-2 protective genotypes are more susceptible to neuroblastoma than those with 3-4 protective genotypes (adjusted OR=0.71, 95% CI=0.53-0.97, P=0.028). Moreover, the rs2267755 C>T is significantly associated with messenger RNA (mRNA) expression of ALKBH1 and three of its surrounding genes, including SNWQ, ADCK1, and RPL21P10. These results suggest that the rs2267755 C>T may be a genetic variant to reduce neuroblastoma risk.

Diagnostic yield and novel candidate genes by next generation sequencing in 166 children with intrahepatic cholestasis.

BACKGROUND AND AIMS: Cholestatic liver disease is a leading referral to pediatric liver transplant centers. Inherited disorders are the second most frequent cause of cholestasis in the first month of life. METHODS: We retrospectively characterized the genotype and phenotype of 166 participants with intrahepatic cholestasis, and re-analyzed phenotype and whole-exome sequencing (WES) data from patients with previously undetermined genetic etiology for newly published genes and novel candidates. Functional validations of selected variants were conducted in cultured cells. RESULTS: Overall, we identified disease-causing variants in 31% (52/166) of our study participants. Of the 52 individuals, 18 (35%) had metabolic liver diseases, 9 (17%) had syndromic cholestasis, 9 (17%) had progressive familial intrahepatic cholestasis, 3 (6%) had bile acid synthesis defects, 3(6%) had infantile liver failure and 10 (19%) had a phenocopy of intrahepatic cholestasis. By reverse phenotyping, we identified a de novo variant c.1883G > A in FAM111B of a case with high glutamyl transpeptidase (GGT) cholestasis. By re-analyzing WES data, two patients were newly solved, who had compound heterozygous variants in recently published genes KIF12 and USP53, respectively. Our additional search for novel candidates in unsolved WES families revealed four potential novel candidate genes (NCOA6, CCDC88B, USP24 and ATP11C), among which the patients with variants in NCOA6 and ATP11C recapitulate the cholestasis phenotype in mice models. CONCLUSIONS: In a single-center pediatric cohort, we identified monogenic variants in 22 known human intrahepatic cholestasis or phenocopy genes, explaining up to 31% of the intrahepatic cholestasis patients. Our findings suggest that re-evaluating existing WES data from well-phenotyped patients on a regular basis can increase the diagnostic yield for cholestatic liver disease in children.

Clinical characteristics associated with recurrent viral RNA positivity in patients within two weeks after recovering from the first SARS-CoV-2 infection.

Many studies have shown that recovered coronavirus disease 2019 (COVID-19) patients frequently exhibit recurrent viral RNA positivity (RP) for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our study aimed to summarize the clinical characteristics of these patients and explore potential reasons for RP occurrence. We divided 439 participants into four groups based on the severity of illness prior to the COVID-19 recovery and age: mild-child group, moderate-child group, mild-adult group, and moderate-adult group. Laboratory data were collected and statistical analyzed using the SPSS software, version 24.0. Significant differences were observed in age, alanine aminotransferase (ALT), aspartate aminotransferase (AST), C-reactive protein (CRP), interleukin 6 (IL-6), and neutrophil to lymphocyte ratio (NLR) levels between the mild-adult group and the moderate-adult group (P < 0.05). Additionally, AST levels differed significantly between the mild-child group and the moderate-child group (P < 0.05). The proportion of RP patients within the four groups varied from 7.95% to 26.13% within a 2-week period. Logistic regression analysis revealed that younger age and moderate symptoms were risk factors for RP in children, while the presence of comorbidities (such as chronic heart, lung, liver, and kidney diseases), elevated IL-6 levels, and NLR were risk factors for RP in adults. We constructed two predictive models containing these relevant parameters, and the results of the receiver operating characteristic (ROC) curves indicated strong predictive utility. Our findings suggest that younger children with more severe symptoms, as well as adult patients with elevated levels of IL-6 and NLR and underlying diseases, are at higher risk of RP occurrence.

Functional TET2 gene polymorphisms increase the risk of neuroblastoma in Chinese children.

The 5-methylcytosine (m5C) is the key chemical modification in RNAs. As one of the demethylases in m5C, TET2 has been shown as a tumor suppressor. However, the impact of TET2 gene polymorphisms on neuroblastoma has not been elucidated. 402 neuroblastoma patients and 473 controls were genotyped for TET2 gene polymorphisms using the TaqMan method. The impact of TET2 gene polymorphisms on neuroblastoma susceptibility was determined using multivariate logistic regression analysis. We also adopted genotype-tissue expression database to explore the impact of TET2 gene polymorphisms on the expression of host and nearby genes. We used the R2 platform and Sangerbox tool to analyze the relationship between gene expression and neuroblastoma risk and prognosis through non-parametric testing and Kaplan-Meier analysis, respectively. We found the TET2 gene polymorphisms (rs10007915 G > C and rs7670522 A > C) and the combined 2-5 risk genotypes can significantly increase neuroblastoma risk. Stratification analysis showed that these significant associations were more prominent in certain subgroups. TET2 rs10007915 G > C and rs7670522 A > C are significantly associated with reduced expression of TET2 mRNA. Moreover, lower expression of TET2 gene is associated with high risk, MYCN amplification, and poor prognosis of neuroblastoma. The rs10007915 G > C and rs7670522 A > C are significantly related to the increased expression of inorganic pyrophosphatase 2 mRNA, and higher expression of PPA2 gene is associated with high risk, MYCN amplification, and poor prognosis of neuroblastomas. In summary, TET2 rs10007915 G > C and rs7670522 A > C significantly confer neuroblastoma susceptibility, and further research is needed to investigate the underlying mechanisms.

Intervertebral Disk Degeneration and Bone Mineral Density: A Bidirectional Mendelian Randomization Study.

This study aimed to investigate the causal relationship between bone mineral density (BMD) and intervertebral disk degeneration (IVDD) using a two-sample bidirectional Mendelian randomization analysis. Summary-level data from the Genome-Wide Association Study (GWAS) were used. Instrumental variables (IVs) for IVDD were selected from the large-scale Genome-Wide Association Study (GWAS) (20,001 cases and 164,682 controls). Bone mineral density (BMD) at five different sites (heel (n = 426,824), total body (TB) (n = 56,284), forearm (FA) (n = 8143), femoral neck (FN) (n = 32,735), and lumbar spine (LS) (n = 28,498)) was used as a phenotype for OP. Bidirectional causality between IVDD and BMD was assessed using inverse variance weighting (IVW) and other methods. Related sensitivity analyses were performed. Myopia was also analyzed as a negative control result to ensure the validity of IVs. Heel bone mineral density (heel BMD), total body bone mineral density (TB-BMD), femoral neck bone mineral density (FN-BMD), and lumbar spine bone mineral density (LS-BMD) have a direct causal relationship on intervertebral disk degeneration (IVDD) [heel BMD-related analysis: beta = 0.06, p = 0.03; TB-BMD-related analysis: beta = 0.18, p = 8.72E-08; FN-BMD-related analysis: beta = 0.15, p = 4.89E-03; LS-BMD-related analysis: beta = 0.16, p = 1.43E-04]. There was no evidence of a significant causal effect of IVDD on BMD. In conclusion, our study found a significant positive causal effect of lower BMD on IVDD, and we identified significant causal effects of heel, TB-, FN-, and LS-BMD on IVDD, but there was no evidence of a significant causal effect of IVDD on BMD.

The value of age IgG and IL6 in estimating time of viral clearance in asymptomatic or mild patients with COVID-19.

Background: The aim of this study was to investigate the relationship between Age, immunoglobin G (IgG), immunoglobin M (IgM), procalcitonin (PCT), and interleukin-6 (IL6), and the time to clear viral nucleic acids in asymptomatic and mild coronavirus disease 2019 (COVID-19) patients, as well as evaluated the predictive value of these biochemical indicators. Methods: We performed a retrospective analysis on 1,570 individuals who were admitted to Tianjin First Central Hospital and diagnosed with asymptomatic or mild cases. Laboratory data were collected, including age, gender, levels of IgG, IgM, PCT and IL6, as well as results of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) nucleic acid test. These data were statistically analyzed using SPSS software, version 24.0. Results: The results indicated that among mild patients, Age, IgG, and the time to clear viral nucleic acids were higher than asymptomatic patients (p < 0.05). And the time to clear viral nucleic acids was significantly correlated with Age, IgG, IgM, PCT, and IL6 (p < 0.05), IgG (r = -0.445, p < 0.001) showed moderate correlations. Using logistic regression analysis, we identified older age, high IL6 levels, and low IgG levels were risk factors for nucleic acid clearance exceeding 14 days (p < 0.05). When combining these three indicators to predict the probability of nucleic acid clearance exceeding 14 days in the 1,570 patients, the AUROC was found to be 0.727. Conclusion: Age, IgG, and IL6 could potentially serve as useful predictors for nucleic acid clearance exceeding 14 days in asymptomatic and mild COVID-19 patients.

RTEL1 gene polymorphisms and neuroblastoma risk in Chinese children.

BACKGROUND: Neuroblastoma, a neuroendocrine tumor originating from the sympathetic ganglia, is one of the most common malignancies in childhood. RTEL1 is critical in many fundamental cellular processes, such as DNA replication, DNA damage repair, genomic integrity, and telomere stability. Single nucleotide polymorphisms (SNPs) in the RTEL1 gene have been reported to confer susceptibility to multiple cancers, but their contributing roles in neuroblastoma remain unclear. METHODS: We conducted a study on 402 neuroblastoma cases and 473 controls to assess the association between four RTEL1 SNPs (rs3761124 T>C, rs3848672 T>C, rs3208008 A>C and rs2297441 G>A) and neuroblastoma susceptibility. RESULTS: Our results show that rs3848672 T>C is significantly associated with an increased risk of neuroblastoma [CC vs. TT/TC: adjusted odds ratio (OR)=1.39, 95% confidence interval (CI)=1.02-1.90, P=0.038]. The stratified analysis further indicated that boy carriers of the rs3848672 CC genotype had a higher risk of neuroblastoma, and all carriers had an increased risk of developing neuroblastoma of mediastinum origin. Moreover, the rs2297441 AA genotype increased neuroblastoma risk in girls and predisposed children to neuroblastoma arising from retroperitoneal. CONCLUSION: Our study indicated that the rs3848672 CC and rs2297441 AA genotypes of the RTEL1 gene are significantly associated with an increased risk of neuroblastoma in Chinese children in a gender- and site-specific manner.

A toxin-antidote system contributes to interspecific reproductive isolation in rice.

Breakdown of reproductive isolation facilitates flow of useful trait genes into crop plants from their wild relatives. Hybrid sterility, a major form of reproductive isolation exists between cultivated rice (Oryza sativa) and wild rice (O. meridionalis, Mer). Here, we report the cloning of qHMS1, a quantitative trait locus controlling hybrid male sterility between these two species. Like qHMS7, another locus we cloned previously, qHMS1 encodes a toxin-antidote system, but differs in the encoded proteins, their evolutionary origin, and action time point during pollen development. In plants heterozygous at qHMS1, ~ 50% of pollens carrying qHMS1-D (an allele from cultivated rice) are selectively killed. In plants heterozygous at both qHMS1 and qHMS7, ~ 75% pollens without co-presence of qHMS1-Mer and qHMS7-D are selectively killed, indicating that the antidotes function in a toxin-dependent manner. Our results indicate that different toxin-antidote systems provide stacked reproductive isolation for maintaining species identity and shed light on breakdown of hybrid male sterility.

MIR938 rs2505901 T>C polymorphism is associated with increased neuroblastoma risk in Chinese children.

Neuroblastoma (NB) is a kind of childhood cancer that is a prevailing and deadly solid neoplasm among pediatric malignancies. The transcriptional output of MIR938 is capable of participating in the posttranscriptional modulation of gene expression, whereby it exerts its regulatory effect by modulating both the stability and translation of target mRNAs. Previous studies showed that MIR938 was associated with many cancers. Hence, functional genetic variants in the MIR938 can be attributed to NB risk. We recruited 402 neuroblastoma patients and 473 controls from the Children's Hospital of Nanjing Medical University and genotyped one MIR938 single-nucleotide polymorphism (SNP) (rs2505901 T>C). There were significant associations between the rs2505901 T>C and NB risk [CC vs. TT: adjusted odds ratio (OR) = 1.90, 95% confidence interval (CI) = 1.02-3.55, P=0.045; CC vs. TT/TC: adjusted OR = 2.02, 95% CI = 1.09-3.75, P=0.026]. This analysis of genotypes revealed that T>C increased the risk of NB. Some borderline significant different relationships were observed in the stratified analyses: age ≤ 18 months (adjusted OR = 2.95, 95% CI = 0.92-9.51, P=0.070), male sex (adjusted OR = 2.19, 95% CI = 0.95-5.08, P=0.067), and clinical stage III+IV (adjusted OR = 2.12, 95% CI = 0.98-4.56, P=0.055). The present study revealed that the MIR938 rs2505901 T>C polymorphism may be a potential risk factor for neuroblastoma in Chinese children. In the long term, conducting large and diverse sample studies from different ethnicities will indeed be crucial in determining the role of MIR938 polymorphisms in NB risk. By including individuals from various ethnic backgrounds, researchers can account for potential genetic variations that may exist between populations.

A CYP78As-small grain4-coat protein complex â ¡ pathway promotes grain size in rice.

CYP78A, a cytochrome P450 subfamily that includes rice (Oryza sativa L.) BIG GRAIN2 (BG2, CYP78A13) and Arabidopsis thaliana KLUH (KLU, CYP78A5), generate an unknown mobile growth signal (referred to as a CYP78A-derived signal) that increases grain (seed) size. However, the mechanism by which the CYP78A pathway increases grain size remains elusive. Here, we characterized a rice small grain mutant, small grain4 (smg4), with smaller grains than its wild type due to restricted cell expansion and cell proliferation in spikelet hulls. SMG4 encodes a multidrug and toxic compound extrusion (MATE) transporter. Loss of function of SMG4 causes smaller grains while overexpressing SMG4 results in larger grains. SMG4 is mainly localized to endoplasmic reticulum (ER) exit sites (ERESs) and partially localized to the ER and Golgi. Biochemically, SMG4 interacts with coat protein complex Ⅱ (COPⅡ) components (Sar1, Sec23, and Sec24) and CYP78As (BG2, GRAIN LENGTH 3.2 [GL3.2], and BG2-LIKE 1 [BG2L1]). Genetically, SMG4 acts, at least in part, in a common pathway with Sar1 and CYP78As to regulate grain size. In summary, our findings reveal a CYP78As-SMG4-COPⅡ regulatory pathway for grain size in rice, thus providing new insights into the molecular and genetic regulatory mechanism of grain size.

miR-100 rs1834306 a > G polymorphism decreases neuroblastoma risk in Chinese children.

BACKGROUND: Neuroblastoma is a common malignant tumor stemming from the sympathetic nervous system in children, which is often life-threatening. The genetics of neuroblastoma remains unclear. Studies have shown that miRNAs participate in the regulation of a broad spectrum of biological pathways. The abnormity in the miRNA is associated with the risk of various cancers, including neuroblastoma. However, research on the relationship of miRNA polymorphisms with neuroblastoma susceptibility is still in the initial stage. METHODS: In this research, a retrospective case-control study was conducted to explore whether miR-100 rs1834306 A > G polymorphism is associated with neuroblastoma susceptibility. We enrolled 402 cases and 473 controls for the study. The logistic regression analysis was adopted to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between miR-100 rs1834306 A > G and neuroblastoma risk. RESULTS: Our results elucidated that the miR-100 rs1834306 A > G polymorphism was associated with the decreased risk of neuroblastoma (AG versus AA: adjusted OR = 0.72, 95% CI = 0.53-0.98, and P = 0.038). The subsequent stratified analysis further found that rs1834306 AG/GG genotype reduced the risk of neuroblastoma in the subgroup with tumors of the mediastinum origin (adjusted OR = 0.63, 95% CI = 0.41-0.95, and P = 0.029). CONCLUSIONS: In summary, miR-100 rs1834306 A > G polymorphism was shown to associate with decreased neuroblastoma risk in Chinese children, especially for neuroblastoma of mediastinum origin. This conclusion needs to be verified in additional large-size case-control studies.

A natural gene drive system confers reproductive isolation in rice.

Hybrid sterility restricts the utilization of superior heterosis of indica-japonica inter-subspecific hybrids. In this study, we report the identification of RHS12, a major locus controlling male gamete sterility in indica-japonica hybrid rice. We show that RHS12 consists of two genes (iORF3/DUYAO and iORF4/JIEYAO) that confer preferential transmission of the RHS12-i type male gamete into the progeny, thereby forming a natural gene drive. DUYAO encodes a mitochondrion-targeted protein that interacts with OsCOX11 to trigger cytotoxicity and cell death, whereas JIEYAO encodes a protein that reroutes DUYAO to the autophagosome for degradation via direct physical interaction, thereby detoxifying DUYAO. Evolutionary trajectory analysis reveals that this system likely formed de novo in the AA genome Oryza clade and contributed to reproductive isolation (RI) between different lineages of rice. Our combined results provide mechanistic insights into the genetic basis of RI as well as insights for strategic designs of hybrid rice breeding.

Functional polymorphisms of the TET1 gene increase the risk of neuroblastoma in Chinese children.

Common genetic mutations are absent in neuroblastoma, one of the most common childhood tumours. As a demethylase of 5-methylcytosine (m5C) modification, TET1 plays an important role in tumourigenesis and differentiation. However, the association between TET1 gene polymorphisms and susceptibility to neuroblastoma has not been reported. Three TET1 gene polymorphisms (rs16925541 A > G, rs3998860 G > A and rs12781492 A > C) in 402 Chinese patients with neuroblastoma and 473 cancer-free controls were assessed using TaqMan. Multivariate logistic regression analysis was used to evaluate the association between TET1 gene polymorphisms and susceptibility to neuroblastoma. The GTEx database was used to analyse the impact of these polymorphisms on peripheral gene expression. The relationship between gene expression and prognosis was analysed using Kaplan-Meier analysis with the R2 platform. We found that both rs3998860 G > A and rs12781492 A > C were significantly associated with increased neuroblastoma risk. Stratified analysis further showed that rs3998860 G > A and rs12781492 A > C significantly increased neuroblastoma risk in certain subgroups. In the combined risk genotype model, 1-3 risk genotypes significantly increased risk of neuroblastoma compared with the 0 risk genotype. rs3998860 G > A and rs12781492 A > C were significantly associated with increased STOX1 mRNA expression in adrenal and whole blood, and high expression of STOX1 mRNA in adrenal and whole blood was significantly associated with worse prognosis. In summary, TET1 gene polymorphisms are significantly associated with increased neuroblastoma risk; further research is required for the potential mechanism and therapeutic prospects in neuroblastoma.

Effects of vaccines on clinical characteristics of convalescent adult patients infected with SARS-CoV-2 Omicron variant: A retrospective study.

Introduction: The protective effect of SARS-CoV-2 vaccines has become a global focus due to Omicron variant pandemic. The effects of various SARS-CoV-2 vaccines are diverse. However, studies on the effect of domestic vaccines on clinical characteristics in convalescent adult patients infected with the Omicron variant are lacking. Methods: In this retrospective, single-center cohort study, the effect of three domestic vaccines on clinical characteristics of convalescent adult patients infected with the Omicron variant was investigated in the initial largest outbreak of the Omicron variant infection between January and February 2022 in Tianjin, China. The primary endpoint was COVID-19 severity and the secondary endpoints were re-positive results on nucleic acid tests, liver and kidney function, and inflammation levels during recovery. Results: A total of 320 adult patients infected with the Omicron variant were enrolled, including 296 post-vaccination and 24 unvaccinated patients. The median age of the unvaccinated patients was higher than that of vaccinated patients, but no significant difference was detected in the sex composition ratio between the different groups. Binary logistic regression results suggested that Sinopharm and Sinovac vaccine was an independent protective factor for relieving the severity of the Omicron variant infection. Regrettably, the vaccines did not showed any protective effect on the liver and kidney function of convalescent adult patients. Three domestic vaccines significantly relieved inflammation and increased the SARS-CoV-2-specific antibody levels. Furthermore, Sinovac and CanSino vaccines had a better immune stimulation effect on increasing T lymphocytes levels in convalescent adult patients. In addition, three domestic vaccines have protective effects on preventing re-detectable positive (RP) result in convalescent adult patients. Conclusion: Although the three domestic vaccines cannot prevent the infection of the Omicron variant, it has a significant protective effect in adult patients. This study supports the policy of accelerating to vaccination worldwide combat the evolving and mutating SARS-CoV-2. Discussion: Omicron spreads faster and might escape antibodies more readily than previous variants, increasing the cases of reinfection and breakthrough infections in vaccinated people. Although vaccinated people are likely to have a much lower risk of severe disease from Omicron infection, many issues still need to be considered. Concerns about lower vaccine efficacy because of new variants might have changed our understanding of the COVID-19 endgame, disabusing the world of the notion that global vaccination is by itself adequate for controlling SARS-CoV-2 infection. The current data showed that vaccination with three domestic SARS-CoV-2 vaccines alleviates the disease severity of adult patients with COVID-19, reduces the inflammation level and the RP rate of convalescent adult patients, and enhances body's defense against the virus in convalescent adult patients. Moreover, our study has highlighted that a combination prevention approach of vaccination and public health measures would be an effective strategy.