Chromosome-level genome assembly of a cliff plant Taihangia rupestris var. ciliata provides insights into its adaptation and demographic history.

BACKGROUND: Cliffs are recognized as one of the most challenging environments for plants, characterized by harsh conditions such as drought, infertile soil, and steep terrain. However, they surprisingly host ancient and diverse plant communities and play a crucial role in protecting biodiversity. The Taihang Mountains, which act as a natural boundary in eastern China, support a rich variety of plant species, including many unique to cliff habitats. However, it is little known how cliff plants adapt to harsh habitats and the demographic history in this region. RESULTS: To better understand the demographic history and adaptation of cliff plants in this area, we analyzed the chromosome-level genome of a representative cliff plant, T. rupestris var. ciliata, which has a genome size of 769.5 Mb, with a scaffold N50 of 104.92 Mb. The rapid expansion of transposable elements may have contributed to the increasing genome and its ability to adapt to unique and challenging cliff habitats. Comparative analysis of the genome evolution between Taihangia and non-cliff plants in Rosaceae revealed a significant expansion of gene families associated with oxidative phosphorylation, which is likely a response to the abiotic stresses faced by cliff plants. This expansion may explain the long-term adaptation of Taihangia to harsh cliff environments. The effective population size of the two varieties has continuously decreased due to climatic fluctuations during the Quaternary period. Furthermore, significant differences in gene expression between the two varieties may explain the varied leaf phenotypes and adaptations to harsh conditions in different natural distributions. CONCLUSION: Our study highlights the extraordinary adaptation of T. rupestris var. ciliata, shedding light on the evolution of cliff plants worldwide.

Identifying potential imaging markers for diffusion property changes in a mouse model of amyotrophic lateral sclerosis: Application of the continuous time random walk model to ultrahigh b-value diffusion-weighted MR images of spinal cord tissue.

Diffusion MRI (dMRI) explores tissue microstructures by analyzing diffusion-weighted signal decay measured at different b-values. While relatively low b-values are used for most dMRI models, high b-value diffusion-weighted imaging (DWI) techniques have gained interest given that the non-Gaussian water diffusion behavior observed at high b-values can yield potentially valuable information. In this study, we investigated anomalous diffusion behaviors associated with degeneration of spinal cord tissue using a continuous time random walk (CTRW) model for DWI data acquired across an extensive range of ultrahigh b-values. The diffusion data were acquired in situ from the lumbar level of spinal cords of wild-type and age-matched transgenic SOD1G93A mice, a well-established animal model of amyotrophic lateral sclerosis (ALS) featuring progressive degeneration of axonal tracts in this tissue. Based on the diffusion decay behaviors at low and ultrahigh b-values, we applied the CTRW model using various combinations of b-values and compared diffusion metrics calculated from the CTRW model between the experimental groups. We found that diffusion-weighted signal decay curves measured with ultrahigh b-values (up to 858,022 s/mm2 in this study) were well represented by the CTRW model. The anomalous diffusion coefficient obtained from lumbar spinal cords was significantly higher in SOD1G93A mice compared with control mice (14.7 × 10-5 ± 5.54 × 10-5  vs. 7.87 × 10-5 ± 2.48 × 10-5  mm2 /s, p = 0.01). We believe this is the first study to illustrate the efficacy of the CTRW model for analyzing anomalous diffusion regimes at ultrahigh b-values. The CTRW modeling of ultrahigh b-value dMRI can potentially present a novel approach for noninvasively evaluating alterations in spinal cord tissue associated with ALS pathology.

Whole genome resequencing-based analysis of plateau adaptation in Meiren yak (Bos grunniens).

The Meiren yak is an important genetic resource in Gansu Province, China. In this study, we aimed to explore the evolutionary history and population structure of the genetic resource of Meiren yak and to mine the characteristic genes of Meiren yak. We analysed a total of 93 yaks of eight yak breeds based on whole genome resequencing combined with population genomics and used θπ ratio and Fst method to screen the selected sites in the genome region. The results proved that Meiren yak can be used as a potential genetic resource in Gansu Province. The genes in Meiren yak with positive selection in selection signal analysis were subjected to the Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses, which indicated that the genes were related to the adaptability to high altitude and hypoxic environment. By analysing the genetic variation of Meiren yak at the genome-wide level, this study provided a theoretical basis for genetic improvement of Meiren yak and for the development of high-quality yak resources.

Potential mechanisms of hexaconazole resistance in Fusarium graminearum.

The Fusarium head blight (FHB) caused by Fusarium graminearum is a serious fungal disease that can dramatically impact wheat production. At present, control is mainly achieved by the use of chemical fungicides. Hexaconazole (IUPAC name: 2-(2,4-dichlorophenyl)-1-(1,2,4-triazol-1-yl)hexan-2-ol) is a widely used triazole fungicide, but the sensitivity of F. graminearum to this compound has yet to be established. The current study found that the EC50 values of 83 field isolates of F. graminearum ranged between 0.06 and 4.33 µg/mL, with an average EC50 of 0.78 µg/mL. Assessment of four hexaconazole-resistant laboratory mutants of F. graminearum revealed that their mycelial growth, and pathogenicity were reduced compared to their parental isolates, and that asexual reproduction was reduced by resistance to hexaconazole. Meanwhile, the mutants appeared to be more sensitive to abiotic stress associated with SDS, and H2O2, while their tolerance of high concentration of Congo red, and Na+ and K+ increased. Molecular analysis revealed numerous point mutations in the FgCYP51 target genes that resulted in amino acid substitutions, including L92P and N123S in FgCYP51A, as well as M331V, F62L, Q252R, A412V, and V488A in FgCYP51B, and S28L, S256A, V307A, D287G and R515I in FgCYP51C, three of which (S28L, S256A, and V307A) were conserved in all of the resistant mutants. Furthermore, the expression of the FgCYP51 genes in resistant strains was found to be significantly (p < 0.05) reduced compared to their sensitive parental isolates. Positive cross-resistance was found between hexaconazole and metconazole and flutriafol, as well as with the diarylamine fungicide fluazinam, but not with propiconazole, and the phenylpyrrole fungicide fludioxonil, or with tebuconazole, which actually exhibited negative cross-resistance. These results provide valuable insight into resistant mechanisms to triazole fungicides in F. graminearum, as well as the appropriate selection of fungicide combinations for the control of FHB to ensure optimal wheat production.

Deferoxamine prevents poststroke memory impairment in female diabetic rats: potential links to hemorrhagic transformation and ferroptosis.

Diabetes increases the risk of poststroke cognitive impairment (PSCI). Greater hemorrhagic transformation (HT) after stroke is associated with vasoregression and cognitive decline in male diabetic rats. Iron chelator deferoxamine (DFX) prevents vasoregression and improves outcomes. Although diabetic female rats develop greater HT, its impact on poststroke cerebrovascularization and cognitive outcomes remained unknown. We hypothesized that diabetes mediates pathological neovascularization, and DFX attenuates poststroke cerebrovascular remodeling and improves neurological outcomes in female diabetic rats. Female control and diabetic animals were treated with DFX or vehicle for 7 days after stroke. Vascular indices, microglial activation, and blood-brain barrier (BBB) integrity were evaluated on day 14. Results from diabetic female rats were partially compared with our previously published findings in male counterparts. Hemin-induced programmed cell death was studied in male and female brain microvascular endothelial cell lines (BMVEC). There was no vasoregression after stroke in either control or diabetic female animals. DFX prevented diabetes-mediated gliovascular remodeling and compromised BBB integrity while improving memory function in diabetes. Comparisons of female and male rats indicated sex differences in cognitive and vascular outcomes. Hemin mediated ferroptosis in both male and female BMVECs. DFX improved survival but had differential effects on ferroptosis signaling in female and male cells. These results suggest that stroke and associated HT do not affect cerebrovascularization in diabetic female rats, but iron chelation may provide a novel therapeutic strategy in the prevention of poststroke memory impairment in females with diabetes via the preservation of gliovascular integrity and improvement of endothelial cell survival.NEW & NOTEWORTHY The current study shows for the first time that diabetes does not promote aberrant cerebrovascularization in female rats. This contrasts with what we reported in male animals in various diabetes models. Deferoxamine preserved recognition memory function in diabetic female animals after stroke. The effect(s) of stroke and deferoxamine on cerebrovascular density and microglial activation also appear(s) to be different in female diabetic rats. Lastly, deferoxamine exerts detrimental effects on animals and BMVECs under control conditions.

Independent effects of the triglyceride-glucose index on all-cause mortality in critically ill patients with coronary heart disease: analysis of the MIMIC-III database.

BACKGROUND: The triglyceride-glucose (TyG) index is a reliable alternative biomarker of insulin resistance (IR). However, whether the TyG index has prognostic value in critically ill patients with coronary heart disease (CHD) remains unclear. METHODS: Participants from the Medical Information Mart for Intensive Care III (MIMIC-III) were grouped into quartiles according to the TyG index. The primary outcome was in-hospital all-cause mortality. Cox proportional hazards models were constructed to examine the association between TyG index and all-cause mortality in critically ill patients with CHD. A restricted cubic splines model was used to examine the associations between the TyG index and outcomes. RESULTS: A total of 1,618 patients (65.14% men) were included. The hospital mortality and intensive care unit (ICU) mortality rate were 9.64% and 7.60%, respectively. Multivariable Cox proportional hazards analyses indicated that the TyG index was independently associated with an elevated risk of hospital mortality (HR, 1.71 [95% CI 1.25-2.33] P = 0.001) and ICU mortality (HR, 1.50 [95% CI 1.07-2.10] P = 0.019). The restricted cubic splines regression model revealed that the risk of hospital mortality and ICU mortality increased linearly with increasing TyG index (P for non-linearity = 0.467 and P for non-linearity = 0.764). CONCLUSIONS: The TyG index was a strong independent predictor of greater mortality in critically ill patients with CHD. Larger prospective studies are required to confirm these findings.

Interaction between PD-L1 and soluble VEGFR1 in glioblastoma-educated macrophages.

PURPOSE: The combined application of immune checkpoint inhibitors (ICIs) and anti-angiogenesis therapy has shown synergistic effects on glioblastoma (GBM). As important resources of PD-L1 in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) have significant impact of the efficiency of ICIs. However, the effects of anti-angiogenesis agents on immune checkpoints expression are not fully understood. METHOD: GBM-educated macrophages were generated from circulating monocytes of healthy controls and GBM patients under the education of GBM cell line. Surface expression of PD-L1 and VEGFR1 on GBM-educated macrophages was analyzed. VEGFR1 NAb and soluble VEGFR1 (sVEGFR1) were added and their effects on PD-L1 expression on TAMs was investigated. Serum soluble PD-L1 (sPD-L1) and sVEGFR1 levels in GBM patients were measured and their correlation was analyzed. RESULT: The expression intensity of PD-L1 on GBM-educated macrophages was higher and its up-regulation partially depends on VEGFR1 signaling pathway. GBM-educated macrophages secreted less levels of soluble VEGFR1 (sVEGFR1), and exogenous sVEGFR1 down-regulated PD-L1 expression intensity. PD-L1 blockade promoted the secretion of sVEGFR1. Finally, sVEGFR1 and sPD-L1 in serum of GBM patients were overexpressed, and a positive correlation was found. CONCLUSION: These findings reveal the interaction between PD-L1 and VEGFR1 signaling pathway in GBM-educated macrophages. VEGFR1 is involved with PD-L1 overexpression, which can be impeded by autocrine regulation of sVEGFR1. sVEGFR1 secretion by GBM-educated macrophages can be promoted by PD-L1 blockade. Taken together, these findings provide evidences for the combined application of ICIs and anti-angiogenesis therapies in the treatment of GBM.

The TICE Pathway: Mechanisms and Potential Clinical Applications.

PURPOSE OF REVIEW: Transintestinal cholesterol excretion (TICE) is a non-biliary pathway that excretes excess cholesterol from the body through feces. This article focuses on the research progress of the TICE pathway in the last few years, including the discovery process of the TICE pathway, its molecular mechanism, and potential clinical applications. RECENT FINDINGS: Cholesterol homeostasis is vital for cardiovascular diseases, stroke, and neurodegenerative diseases. Beyond the cholesterol excretion via hepatobiliary pathway, TICE contributes significantly to reverse cholesterol transport ex vivo and in vivo. Nuclear receptors are ligand-activated transcription factors that regulate cholesterol metabolism. The farnesoid X receptor (FXR) and liver X receptor (LXR) activated, respectively, by oxysterols and bile acids promote intestinal cholesterol secretion through ABCG5/G8. Nutrient regulators and intestinal flora also modulate cholesterol secretion through the TICE pathway. TICE allows direct elimination of plasma cholesterol, which may provide an attractive therapeutic targets. TICE pathway may provide a potential target to stimulate cholesterol elimination and reduce the risk of cardiovascular diseases.

Bacteriophage-based techniques for elucidating the function of zebrafish gut microbiota.

Bacteriophages (or phages) are unique viruses that can specifically infect bacteria. Since their discovery by Twort and d'Herelle, phages with bacterial specificity have played important roles in microbial regulation. The intestinal microbiota and host health are intimately linked with nutrient, metabolism, development, and immunity aspects. However, the mechanism of interactions between the composition of the microbiota and their functions in maintaining host health still needs to be further explored. To address the lack of methodology and functions of intestinal microbiota in the host, we first proposed that, with the regulations of special intestinal microbiota and applications of germ-free (GF) zebrafish model, phages would be used to infect and reduce/eliminate the defined gut bacteria in the conventionally raised (CR) zebrafish and compared with the GF zebrafish colonized with defined bacterial strains. Thus, this review highlighted the background and roles of phages and their functional characteristics, and we also summarized the phage-specific infection of target microorganisms, methods to improve the phage specificity, and their regulation within the zebrafish model and gut microbial functional study. Moreover, the primary protocol of phage therapy to control the intestinal microbiota in zebrafish models from larvae to adults was recommended including phage screening from natural sources, identification of host ranges, and experimental design in the animal. A well understanding of the interaction and mechanism between phages and gut bacteria in the host can potentially provide powerful strategies or techniques for preventing bacteria-related human diseases by precisely regulating in vitro and in vivo, which will provide novel insights for phages' application and combined research in the future. KEY POINTS: • Zebrafish models for clarifying the microbial and phages' functions were discussed • Phages infect host bacteria with exquisite specificity and efficacy • Phages can reduce/eliminate the defined gut bacteria to clarify their function.

Efficacy and safety of liraglutide in patients with type 2 diabetes mellitus and severe obstructive sleep apnea.

OBJECTIVES: To observe the efficacy and side effects of liraglutide in the treatment of type 2 diabetes mellitus (T2DM) patients with severe obstructive sleep apnea (OSA). METHODS: The study conducted in an outpatient setting was a two-center, prospective randomized controlled study. T2DM patients with severe OSA were randomized to the control group (continuous positive airway pressure [CPAP] and drug treatment without liraglutide) or the liraglutide group (CPAP and drug treatment including liraglutide). Demographic and clinical characteristics, sleep-disordered breathing indices, cardiac function indices, and side effects were evaluated and compared between the two groups before and after 3 months. RESULTS: Of 90 patients, 45 were randomized to the intervention arm (with liraglutide) and 45 to the control arm (without liraglutide). One patient in the liraglutide group dropped out of the study on day 8 after enrollment due to obvious gastrointestinal symptoms. No significant differences were found between the two groups in baseline demographics, clinical characteristics, cardiac function indicators, or sleep disorder respiratory indices (P > 0.05). After 3 months, the body mass index (BMI), apnea hypopnea index (AHI), and mean systolic blood pressure in the liraglutide treatment group were significantly lower than those in the control group (P < 0.05). The minimum oxygen saturation was significantly higher in the liraglutide group compared with that in the control group after 3 months of follow-up (P < 0.05). No difference was found between the two groups in the summary of side effects (P > 0.05). CONCLUSIONS: Liraglutide combined with CPAP can effectively reduce BMI, lower mean systolic blood pressure, and improve AHI scores and hypoxia in T2DM patients with severe OSA. Liraglutide did not increase side effects.

Achievements and perspectives of synthetic biology in botanical insecticides.

Botanical insecticides are the origin of all insecticidal compounds. They have been widely used to control pests in crops for a long time. Currently, the commercial production of botanical insecticides extracted from plants is limited because of insufficient raw material supply. Synthetic biology is a promising and effective approach for addressing the current problems of the production of botanical insecticides. It is an emerging biological research hotspot in the field of botanical insecticides. However, the biosynthetic pathways of many botanical insecticides are not completely elucidated. On the other hand, the cytotoxicity of botanical pesticides and low efficiency of these biosynthetic enzymes in new hosts make it still challenging for their heterologous production. In the present review, we summarized the recent developments in the heterologous production of botanical insecticides, analyzed the current challenges, and discussed the feasible production strategies, focusing on elucidating biosynthetic pathways, enzyme engineering, host engineering, and cytotoxicity engineering. Looking to the future, synthetic biology promises to further advance heterologous production of more botanical pesticides.

Impact of diabetes and ischemic stroke on the cerebrovasculature: A female perspective.

There is a very complex interaction between the brain and the cerebral vasculature to meet the metabolic demands of the brain for proper function. Preservation of vascular networks and cerebrovascular function ultimately plays a key role in this intricate communication within the brain in health and disease. Experimental evidence showed that diabetes not only affects the architecture of cerebral blood arteries causing adverse remodeling, pathological neovascularization, and vasoregression, but also alters cerebrovascular function resulting in compromised myogenic reactivity and endothelial dysfunction. Coupled with the disruption of blood brain barrier (BBB) integrity, changes in blood flow and microbleeds into the brain can rapidly occur. When an ischemic insult is superimposed on this pathology, not only is the neurovascular injury greater, but repair mechanisms fail, resulting in greater physical and cognitive deficits. While clinically it is known that women suffer disproportionately from diabetes as well as ischemic stroke and post-stroke cognitive impairment, the cerebrovascular architecture, patho/physiology, as well as cerebrovascular contributions to stroke recovery in female and diabetic animal models are inadequately studied and highlighted in this review.

Potential G-quadruplexes within the Promoter Nuclease Hypersensitive Sites of the Heat-Responsive Genes in Rice.

G-quadruplexes (G4s) have been shown to be involved in the regulation of multiple cellular processes. Exploring putative G4-forming sequences (PQSs) in heat-responsive genes of rice and their folding structures under different conditions will help to understand the mechanism in response to heat stress. In this work, we discovered a prevalence of PQSs in nuclease hypersensitive sites within the promoters of heat-responsive genes. Moreover, 50 % of the searched G3 PQSs ((G3+ L1-7 )3+ G3+ ) locate in heat shock transcription factors. Circular dichroism spectroscopy, thermal difference spectroscopy, and UV melting analysis demonstrated the representative PQSs could adopt stable G4s at physiological temperature and potassium concentration. These PQSs were able to stall Klenow fragment (KF) DNA polymerase by the formation of G4s. However, the G4s with Tm values around 50-60 °C could be increasingly unwound by KF with the increase of temperatures from 25 to 50 °C, implying that these G4s could sense the changes in temperature by structural switch. This work offers fresh clues to understanding the potential of G4-involved functions of PQSs and the molecular events in plants in response to heat stress.

Phase-independent thermometry by Z-spectrum MR imaging.

PURPOSE: Z-spectrum imaging, defined as the consecutive collection of images after saturating over a range of frequency offsets, has been recently proposed as a method to measure the fat-water fraction by the simultaneous detection of fat and water resonances. By incorporating a binomial pulse irradiated at each offset before the readout, the spectral selectivity of the sequence can be further amplified, making it possible to monitor the subtle proton resonance frequency shift that follows a change in temperature. METHODS: We tested the hypothesis in aqueous and cream phantoms and in healthy mice, all under thermal challenge. The binomial module consisted of 2 sinc-shaped pulses of opposite phase separated by a delay. Such a delay served to spread out off-resonance spins, with the resulting excitation profile being a periodic function of the delay and the chemical shift. RESULTS: During heating experiments, the water resonance shifted downfield, and by fitting the curve to a sine function it was possible to quantify the change in temperature. Results from Z-spectrum imaging correlated linearly with data from conventional MRI techniques like T1 mapping and phase differences from spoiled GRE. CONCLUSION: Because the measurement is performed solely on magnitude images, the technique is independent of phase artifacts and is therefore applicable in mixed tissues (e.g., fat). We showed that Z-spectrum imaging can deliver reliable temperature change measurement in both muscular and fatty tissues.

Triglyceride-glucose index linked to all-cause mortality in critically ill patients: a cohort of 3026 patients.

BACKGROUND: Triglyceride-glucose (TyG) index as a reliable surrogate of insulin resistance (IR) has been shown to be related to adverse clinical outcomes in patients with acute coronary syndrome, heart failure, ischemic stroke and so on. However, the relationship between TyG index and all-cause mortality in intensive care unit (ICU) patients remains unknown. The purpose of this study was to investigate the correlation between TyG index and all-cause mortality to evaluate the impact of IR on the prognosis of this population. METHODS: This was a retrospective observational study that included 3026 patients who had an initial triglyceride and glucose data on the first day of ICU admission, and all data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. These patients were grouped into quartiles (Q1-Q4) according to TyG index. The Kaplan-Meier analysis was used to compare all-cause mortality among the above four groups. Cox proportional hazards analyses were performed to examine the association between TyG index and all-cause mortality. RESULTS: During 10.46 years of follow-up, 1148 (37.9%) patients died, of which 350 (11.6%) occurred during the hospital stay and 258 (8.5%) occurred during the ICU stay. Kaplan-Meier analysis showed that the risk of all-cause mortality was significantly higher in patients with higher TyG index (log-rank P = 0.021). Multivariable Cox proportional hazards analyses showed that the TyG index was an independent risk predictor of ICU death (HR: 1.72, 95% CI 1.18-2.52, P = 0.005) and hospital death (HR: 2.19, 95% CI 1.59-3.03, P < 0.001), and each 1-unit increased in the TyG index, a 1.19-fold increase in the risk of death during the hospital stay. CONCLUSIONS: TyG index is strongly related to the all-cause mortality increasing in critically ill patients. This finding indicates that the TyG index might be useful in identifying people at high risk of ICU death and hospital death.

Magnetic resonance imaging reveals microemboli-mediated pathological changes in brain microstructure in diabetic rats: relevance to vascular cognitive impairment/dementia.

Diabetes doubles the risk of vascular cognitive impairment, but the underlying reasons remain unclear. In the present study, we determined the temporal and spatial changes in the brain structure after microemboli (ME) injection using diffusion MRI (dMRI). Control and diabetic rats received cholesterol crystal ME (40-70 µm) injections. Cognitive tests were followed up to 16 weeks, while dMRI scans were performed at baseline and 12 weeks post-ME. The novel object recognition test had a lower d2 recognition index along with a decrease in spontaneous alternations in the Y maze test in diabetic rats with ME. dMRI showed that ME injection caused infarction in two diabetic animals (n=5) but none in controls (n=6). In diabetes, radial diffusivity (DR) was increased while fractional anisotropy (FA) was decreased in the cortex, indicating loss of tissue integrity and edema. In the dorsal hippocampus, mean diffusivity (MD), axial diffusivity (DA), and DR were significantly increased, indicating loss of axons and myelin damage. Histological analyses confirmed more tissue damage and microglial activation in diabetic rats with ME. These results suggest that ME injury and associated cerebrovascular dysfunction are greater in diabetes, which may cause cognitive deficits. Strategies to improve vascular function can be a preventive and therapeutic approach for vascular cognitive impairment.

Methodology and experiences of rapid advice guideline development for children with COVID-19: responding to the COVID-19 outbreak quickly and efficiently.

BACKGROUND: Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to public health emergencies by developing evidence-based recommendations in a short period of time with a scientific and standardized approach. However, the experience from the development process of a RAG has so far not been systematically summarized. Therefore, our working group will take the experience of the development of the RAG for children with COVID-19 as an example to systematically explore the methodology, advantages, and challenges in the development of the RAG. We shall propose suggestions and reflections for future research, in order to provide a more detailed reference for future development of RAGs. RESULT: The development of the RAG by a group of 67 researchers from 11 countries took 50 days from the official commencement of the work (January 28, 2020) to submission (March 17, 2020). A total of 21 meetings were held with a total duration of 48 h (average 2.3 h per meeting) and an average of 16.5 participants attending. Only two of the ten recommendations were fully supported by direct evidence for COVID-19, three recommendations were supported by indirect evidence only, and the proportion of COVID-19 studies among the body of evidence in the remaining five recommendations ranged between 10 and 83%. Six of the ten recommendations used COVID-19 preprints as evidence support, and up to 50% of the studies with direct evidence on COVID-19 were preprints. CONCLUSIONS: In order to respond to public health emergencies, the development of RAG also requires a clear and transparent formulation process, usually using a large amount of indirect and non-peer-reviewed evidence to support the formation of recommendations. Strict following of the WHO RAG handbook does not only enhance the transparency and clarity of the guideline, but also can speed up the guideline development process, thereby saving time and labor costs.

Genome-wide association study and genomic prediction for yield and grain quality traits of hybrid rice.

Genomic selection is an efficient tool for breeding selection, especially for quantitative traits controlled by multiples genes with low heritability. To validate the application of genomic selection in hybrid rice breeding, the yield and grain quality traits of 404 hybrid rice breeding lines were investigated, and the same accessions were genotyped by using a 56 K SNP chip. There were wide variances among the tested accessions for all the measured traits, and most of the traits were correlated. A total of 67 significant loci were identified for the yield-related traits, and 123 significant loci were identified for the grain quality traits by GWAS. Two of these loci associated with increasing grain yield but decreasing grain quality. The GEBVs of all the yield and grain quality traits were calculated by using 15 different prediction algorithms. The plant height, panicle length, thousand grain weight, grain length and width ratio, amylose content, and alkali value have higher predictability than other traits. However, the predictive accuracy of different GS models is different for different traits. This study provided useful information for genomic selection of specific trait using proper markers and prediction models. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01289-6.

SMN and symmetric arginine dimethylation of RNA polymerase II C-terminal domain control termination.

The carboxy-terminal domain (CTD) of the RNA polymerase II (RNAP II) subunit POLR2A is a platform for modifications specifying the recruitment of factors that regulate transcription, mRNA processing, and chromatin remodelling. Here we show that a CTD arginine residue (R1810 in human) that is conserved across vertebrates is symmetrically dimethylated (me2s). This R1810me2s modification requires protein arginine methyltransferase 5 (PRMT5) and recruits the Tudor domain of the survival of motor neuron (SMN, also known as GEMIN1) protein, which is mutated in spinal muscular atrophy. SMN interacts with senataxin, which is sometimes mutated in ataxia oculomotor apraxia type 2 and amyotrophic lateral sclerosis. Because POLR2A R1810me2s and SMN, like senataxin, are required for resolving RNA-DNA hybrids created by RNA polymerase II that form R-loops in transcription termination regions, we propose that R1810me2s, SMN, and senataxin are components of an R-loop resolution pathway. Defects in this pathway can influence transcription termination and may contribute to neurodegenerative disorders.

Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review.

The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that after the treatment, 54.7% (95%CI, 10.3 to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2 to 10.1%) died, and 27.0% (95%CI, 0 to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone. CONCLUSIONS: Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines. WHAT IS KNOWN: • The efficacy and safety of using potential drugs such as remdesivir, glucocorticoid, and intravenous immunoglobulin (IVIG) in treating children and adolescents with COVID-19/MIS-C are unclear. WHAT IS NEW: • Overall, the current evidence cannot adequately demonstrate the effectiveness and safety of using remdesivir, glucocorticoids, and IVIG in treating children and adolescents with COVID-19 or MIS-C. • We are calling for the publication of high-quality clinical trials and provide substantial evidence for the development of guidelines.