Effects of fuel and driving conditions on particle number emissions of China-VI gasoline vehicles: based on corrections to test results.

The increasing number of vehicles are emitting a large amount of particles into the atmosphere, causing serious harm to the ecological environment and human health. This study conducted the Worldwide Harmonized Light Vehicles Test Cycle (WLTC) to investigate the emission characteristics of particle number (PN) of China-VI gasoline vehicles with different gasoline. The gasoline with lower aromatic hydrocarbons and olefins reduced particulate matter (PM) and PN emissions by 24% and 52% respectively. The average PN emission rate of the four vehicles during the first 300 s (the cold start period) was 7.2 times that of the 300 s-1800s. Additionally, because the particle transmission time and instrument response time, the test results of instantaneous emissions of PN were not synchronized with vehicle specific power (VSP). By calculating the Spearman correlation coefficient between pre-average vehicle specific power (PAVSP) and the test results of PN instantaneous emissions, the delay time was determined as 10s. After the PN emissions results were corrected, the PN emissions were found to be more related to VSP. By analyzing the influence of driving status on emission, this study found that vehicles in acceleration mode increased PN emissions by 76% compared to those in constant speed mode.

GateView: A Multi-Omics Platform for Gene Feature Analysis of Virus Receptors within Human Normal Tissues and Tumors.

Viruses are obligate intracellular parasites that rely on cell surface receptor molecules to complete the first step of invading host cells. The experimental method for virus receptor screening is time-consuming, and receptor molecules have been identified for less than half of known viruses. This study collected known human viruses and their receptor molecules. Through bioinformatics analysis, common characteristics of virus receptor molecules (including sequence, expression, mutation, etc.) were obtained to study why these membrane proteins are more likely to become virus receptors. An in-depth analysis of the cataloged virus receptors revealed several noteworthy findings. Compared to other membrane proteins, human virus receptors generally exhibited higher expression levels and lower sequence conservation. These receptors were found in multiple tissues, with certain tissues and cell types displaying significantly higher expression levels. While most receptor molecules showed noticeable age-related variations in expression across different tissues, only a limited number of them exhibited gender-related differences in specific tissues. Interestingly, in contrast to normal tissues, virus receptors showed significant dysregulation in various types of tumors, particularly those associated with dsRNA and retrovirus receptors. Finally, GateView, a multi-omics platform, was established to analyze the gene features of virus receptors in human normal tissues and tumors. Serving as a valuable resource, it enables the exploration of common patterns among virus receptors and the investigation of virus tropism across different tissues, population preferences, virus pathogenicity, and oncolytic virus mechanisms.

Systematic review and network meta-analysis of re-intervention rates of new surgical interventions for benign prostatic hyperplasia.

OBJECTIVE: To assess the re-intervention rates of new surgical benign prostatic hyperplasia (BPH) interventions, as the clinical durability of new surgical interventions for BPH is not widely known. METHODS: A critical review of new surgical BPH therapies namely 'UroLift®', 'Aquablation', 'Rezum', 'prostatic artery embolisation (PAE)' and 'temporary implantable nitinol device (iTIND)' was performed on PubMed, the Cochrane Library, and Embase databases between May 2010 and December 2022 according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statement. All relevant articles were reviewed, and the risk of bias was evaluated using the Cochrane risk assessment tool and Newcastle-Ottawa Scale. RESULTS: Of the 32 studies included, there were 10 randomised controlled trials and 22 prospective observational cohorts. A total of 2400 participants were studied with a median patient age of 66 years, a median prostate volume of 51.9 mL, and a median International Prostate Symptom Score of 22. The lowest re-intervention rate at 12 months was for Aquablation at 0.01%, followed by Rezum at 0.02%, iTIND at 0.03%, and PAE at 0.05%. Network meta-analysis (NMA) showed that the best-ranked treatment at 12 months was transurethral resection of the prostate (TURP), followed by Aquablation, iTIND, Rezum, and UroLift. Re-intervention rates with these new BPH interventions are comparable, although some interventions reported better outcomes than TURP in the shorter term. CONCLUSIONS: While this systematic review and NMA showed that the re-intervention rate with these new surgical BPH interventions appears to be comparable to TURP in the short term, further studies are required to directly compare these various BPH procedures.

Is detrusor overactivity with detrusor underactivity limited to the elderly?

OBJECTIVE: Detrusor overactivity with detrusor underactivity (DO-DU) is classically described in frail institutionalized elderly patients, but we have also observed this diagnosis in younger populations. This research aims to identify the differences between two age groups of DO-DU patients. MATERIALS AND METHODS: This study included DO-DU patients from a single center from 2012 to 2023. Patients were divided into two groups: the "Younger" group (aged less than 70 years) and the "Older" group (aged 70 years or older). We separately compared demographics, the number of risk factors considered to affect bladder function, clinical presentations, and urodynamic findings between these two groups in each gender. RESULTS: There were 210 patients included in the analysis, with 50.48% in the younger group and 49.52% in the older group. The median ages of males and females in the younger group were 57 and 62 years, whereas the median ages of males and females in the older group were 76.5 and 76 years. Multiple sclerosis exhibited statistically significant prevalence in the younger patients (7.7% vs. 0%, p = 0.03 in males and 19.9% vs. 4.6% in females). While diabetes mellitus (DM) was more prevalent in the older males (20.0% vs. 4.6%, p = 0.01), transabdominal hysterectomy was more common in the younger females (46.3% vs. 25%, p = 0.04). 69.8% of the younger group and 71.2% of the older group have at least one risk factor that impact their bladder function. There was no statistically significant difference between the two groups across various risk factor categories. The older males reported a higher incidence of urgency (78.3% vs. 58.5%, p = 0.02) and urge incontinence (61.7% vs. 32.3%, p < 0.01), while the younger females reported a higher incidence of straining during voiding on history (46.3% vs. 20.5%, p = 0.01). The younger males exhibited a greater volume of strong desire to void (385 vs. 300 mL, p = 0.01), maximal cystometric capacity (410 vs. 300 mL, p < 0.01), and a lower highest detrusor overactivity (DO) pressure (37 vs. 50.5 cmH2O, p = 0.02). The younger group had a higher postvoid residual (170 vs. 85 mL in males, p < 0.01 and 180 vs. 120 mL in females, p = 0.02). The voiding efficiency was lower in younger females (40% vs. 60%, p = 0.02). In both ages, the ICS detrusor contraction index and projected isovolumetric pressure 1 were similar. However, without considering risk factors, the older males had the highest DO pressure (57 vs. 29 cmH2O, p < 0.01), and the younger males had a higher voiding pressure (PdetQmax) than the older males (28 vs. 20 cmH2O, p = 0.02). CONCLUSION: DO-DU is not exclusive to elderly patients. It can also be diagnosed in individuals with risk factors regardless of age; therefore, clinicians need a high degree of suspicion, especially in patients who have risk factor(s) for DO and DU. A notable clinical differentiation is that older males diagnosed with DO-DU have a higher incidence of urgency and urge urinary incontinence, while younger females have a higher incidence of straining.

Is There an Optimal Time Window of Placement of Intracranial Pressure (ICP) Monitor for Elderly Patients With Severe Traumatic Brain Injury? An 11-Year Institutional Cohort Study With Restricted Cubic Spline Analysis.

Severe traumatic brain injury (sTBI) is a prominent contributor to both morbidity and mortality in the elderly population. The monitoring of intracranial pressure (ICP) is crucial in the management of sTBI patients. Nevertheless, the appropriate timing for the placement of ICP monitor in elderly sTBI patients remains uncertain. To determine the optimal timing for the placement of ICP monitor in elderly sTBI patients, in this retrospective cohort study, we collected data from elderly patients (> 65 years) who suffered sTBI and received ICP monitors at Tangdu Hospital, The Fourth Military Medical University, between January 2011 and December 2021. To examine the relationship between the time of ICP monitor placement and in-hospital mortality, we conducted a multi-variate-adjusted restricted cubic spline (RCS) analysis. Additionally, logistic regression analysis was applied to further analyze the influencing factors contributing to early or late ICP monitor placements. A total of 283 eligible elderly TBI patients were included in the current analysis. The in-hospital mortality rate was 73 out of 283 (26%). The RCS analysis demonstrated an inverted U-shaped curve in the relationship between the timing of ICP monitor placement and in-hospital mortality. For the elderly sTBI patient cohort, 6 h was identified as the crucial moment for the treatment strategy. In addition, the protective time window for ICP placement was less than 4.92 h for the GCS 3-5 group, and less than 8.26 h for the GCS 6-8 group. However, the clinical benefit of ICP placement decreased gradually over time. The relationship between ICP placement and in-hospital mortality was non-linear, exhibiting an inverted U-shaped curve in elderly patients with sTBI. For elderly patients with sTBI, early (≤ 6 h) ICP placement was associated with reduced in-hospital mortality. The clinical benefit of ICP placement decreased beyond the optimal time window.

Chromosome-level genome assembly of the Japanese sawyer beetle Monochamus alternatus.

The Japanese sawyer beetle Monochamus alternatus (Coleoptera: Cerambycidae) is a pest in pine forests and acts as a vector for the pine wood nematode Bursaphelenchus xylophilus, which causes the pine wilt disease. We assembled a high-quality genome of M. alternatus at the chromosomal level using Illumina, Nanopore, and Hi-C sequencing technologies. The assembled genome is 767.12 Mb, with a scaffold N50 of 82.0 Mb. All contigs were assembled into ten pseudo-chromosomes. The genome contains 63.95% repeat sequences. We identify 16, 284 protein-coding genes in the genome, of which 11,244 were functionally annotated. The high-quality genome of M. alternatus provides an invaluable resource for the biological, ecological, and genetic study of this beetle and opens new avenues for understanding the transmission of pine wood nematode by insect vectors.

A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression.

Human-specific insertions play important roles in human phenotypes and diseases. Here we reported a 446-bp insertion (Insert-446) in intron 11 of the TBC1D8B gene, located on chromosome X, and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome 5. Interestingly, Insert-446 was present in the human Neanderthal and Denisovans genomes, and was fixed in humans after human-chimpanzee divergence. We have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in macaques. In addition, over-expression TBC1D8B promoted cell proliferation and migration through "a dual finger" catalytic mechanism (Arg538 and Gln573) in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in vivo. Knockout of Insert-446 prevented cell proliferation and migration in cancer and normal cells. Our results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B gene. These findings provide a significant insight into the effects of human-specific insertions on evolution.

The mutations on the envelope glycoprotein D contribute to the enhanced neurotropism of the pseudorabies virus variant.

The pseudorabies virus (PRV) TJ strain, a variant of PRV, induces more severe neurological symptoms and higher mortality in piglets and mice than the PRV SC strain isolated in 1980. However, the mechanism underlying responsible for the discrepancy in virulence between these strains remains unclear. Our study investigated the differences in neurotropism between PRV TJ and PRV SC using both in vitro and in vivo models. We discovered that PRV TJ enters neural cells more efficiently than PRV SC. Furthermore, we found that PRV TJ has indistinguishable genomic DNA replication capability and axonal retrograde transport dynamics compared to the PRV SC. To gain deeper insights into the mechanisms underlying these differences, we constructed gene-interchanged chimeric virus constructs and assessed the affinity between envelope glycoprotein B, C, and D (gD) and corresponding receptors. Our findings confirmed that mutations in these envelope proteins, particularly gD, significantly contributed to the heightened attachment and penetration capabilities of PRV TJ. Our study revealed the critical importance of the gDΔR278/P279 and gDV338A in facilitating viral invasion. Furthermore, our observations indicated that mutations in envelope proteins have a more significant impact on viral invasion than on virulence in the mouse model. Our findings provide valuable insights into the roles of natural mutations on the PRV envelope glycoproteins in cell tropism, which sheds light on the relationship between cell tropism and clinical symptoms and offers clues about viral evolution.

A gap-free reference genome reveals structural variations associated with flowering time in rapeseed (Brassica napus).

Allopolyploid oilseed rape (Brassica napus) is an important oil crop and vegetable. However, the latest version of its reference genome, with collapsed duplications, gaps, and other issues, prevents comprehensive genomic analysis. Herein, we report a gap-free assembly of the rapeseed cv. Xiang5A genome using a combination of ONT (Oxford Nanopore Technologies) ultra-long reads, PacBio high-fidelity reads, and Hi-C datasets. It includes gap-free assemblies of all 19 chromosomes and telomere-to-telomere assemblies of eight chromosomes. Compared with previously published genomes of B. napus, our gap-free genome, with a contig N50 length of 50.70 Mb, has complete assemblies of 9 of 19 chromosomes without manual intervention, and greatly improves contiguity and completeness, thereby representing the highest quality genome assembly to date. Our results revealed that B. napus Xiang5A underwent nearly complete triplication and allotetraploidy relative to Arabidopsis thaliana. Using the gap-free assembly, we found that 917 flowering-related genes were affected by structural variation, including BnaA03.VERNALIZATION INSENSITIVE 3 and BnaC04.HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 1. These genes may play crucial roles in regulating flowering time and facilitating the adaptation of Xiang5A in the Yangtze River Basin of China. This reference genome provides a valuable genetic resource for rapeseed functional genomic studies and breeding.

microRNA transcriptome analysis of granulosa cells predicts that the Notch and insulin pathways affect follicular development in chickens.

MicroRNAs (miRNAs) have been documented to play critical roles in chicken reproduction. Granulosa cell (GC) development of the follicle is closely related to hierarchical follicle ordering, making it an important factor in determining laying performance. Thus, it is meaningful to mine follicular development-related miRNAs. To identify regulatory miRNAs and the biological mechanisms by which they control follicular development, we conducted small RNA sequencing of GCs isolated from prehierarchical follicles named small yellow follicle (SYFG), the smallest hierarchical follicle (F6G), and the largest hierarchical follicle (F1G). A total of 99, 196, and 110 differentially expressed miRNAs (DEMs) were identified in SYFG.vs.F6G, SYFG.vs.F1G, and F6G.vs.F1G, respectively. Of these, 22 miRNAs, including miR-223, miR-103a, miR-449c-3p, and miR-203a, were ubiquitously identified as DEMs in three stages. Target gene prediction suggested that these miRNAs are associated with the MAPK, TGF-ß, and Wnt signaling pathways, which are all associated with follicular development. The Notch and insulin signaling pathways were commonly enriched in all three comparisons. RT-qPCR analysis further indicated that the expression levels of PSEN2, which encodes an essential factor regulating Notch and insulin signaling, was significantly changed in SYFG, F6G, and F1G. The current study provides basic data and offers a new foundation for further exploration of the roles of miRNAs in follicular development in chickens.

The Effects of 1-Deoxynojirimycin from Mulberry on Oxidative Stress and Inflammation in Laying Hens and the Direct Effects on Intestine Epithelium Cells In Vitro.

The intestine is highly vulnerable to various factors and has been proposed as a promising determinant for poultry health. Phytogenic or plant-derived feed additives can be used to help improve intestinal health. In this study, we aimed to investigate the effects of DNJ on the antioxidative parameters, including malondialdehyde (MDA), total superoxide dismutase (T-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and inflammatory cytokines (IL-6, IL-1ß, and TNF-α), in plasma and intestinal tissues using layers supplemented with or without the DNJ extract of mulberry leaves (DNJ-E) via the ELISA method. A total of 192 healthy Hy-Line Brown layers, aged 47 weeks old, were used to conduct a 56-day study. All hens were randomly separated into four groups as follows: a basal diet containing 0 mg/kg DNJ-E(CON), 50 mg/kg, 100 mg/kg, and 150 mg/kg DNJ-E. Furthermore, the potential mechanism by which DNJ influences intestinal function was also investigated in in vitro cultured intestinal epithelium cells (IEC) with quantification methods including the use of a cell counting kit-8 (CCK8), ELISA, qRT-PCR, and ROS detection. The results showed that CAT in plasma significantly increased following 50 mg/kg DNJ-E supplementation. Moreover, 50 mg/kg DNJ-E supplementation was associated with increases in T-SOD in the jejunum and ileum. However, there was no significant difference in inflammatory cytokines between groups in in vivo experiments. Subsequent in vitro IEC studies revealed that cell viability increased significantly following 5 µM and 10 µM DNJ treatments while decreasing significantly following 20 µM DNJ treatment. Antioxidative parameters improved at 5 µM and 10 µM DNJ concentrations. However, there were no ameliorative effects on antioxidant parameters observed under 20 µM DNJ treatment. The expression levels of Nrf2 mRNA increased significantly under DNJ treatment. DNJ treatment was associated with significant changes in the expression of genes of inflammatory cytokines. In conclusion, our study revealed that DNJ could improve oxidative stress and inflammation responses in the chicken intestine. These findings provide a theoretical reference for the development of functional feed additives that regulate intestinal health and lay the foundation for systematically revealing the mechanism of DNJ.

Aquablation in men with benign prostate hyperplasia: A systematic review and meta-analysis.

Objective: The aim of the study is to investigate improvements in lower urinary tract symptoms in men with benign prostatic hyperplasia (BPH) treated with prostatic Aquablation. Materials and methods: We performed a literature search of clinical trials using the MEDLINE, Embase, and Cochrane Library databases and retrieved published works on Aquablation for the treatment of BPH up to August 2021. Unpublished works, case reports, conference proceedings, editorial comments, and letters were excluded. Risk of bias was assessed using the ROBINS-I tool. Raw means and mean differences were meta-analyzed to produce summary estimates for pre- versus post-International Prostate Symptom Scores, maximum flow rate, and male sexual health questionnaire value changes. An inverse-variance weighted random effects model was used. Results: Seven studies were included in this review (n = 551 patients) that evaluated various urological parameters. At 3 months, the International Prostate Symptom Scores raw mean difference from baseline was -16.475 (95% confidence interval [CI], -15.264 to -17.686; p < 0.001), with improvements sustained for 12 months. Similarly, maximum flow rate improved by +1.96 (95% CI, 10.015 to 11.878; p < 0.001) from pre to 3 months postoperatively. In addition, the male sexual health questionnaire change pooled effect size was -0.55 (95% CI, -1.621 to 0.531; p = 0.321) from preintervention to postintervention at 3 months. Meta-analyses of some outcomes showed large statistical heterogeneity or evidence of publication bias. Conclusions: Aquablation seems to improve lower urinary tract symptoms in men with BPH while providing relatively preserved sexual function. Further research is required to confirm these preliminary results.

The effect of multiple factors on water-soluble inorganic ions in diesel particulate matter emissions.

The water-soluble inorganic ions (WSII) in diesel particulate matter (DPM) have a significant impact on ambient air quality and human health. In this study, the 12 groups of bench tests were conducted to analyze the emission characteristics of two diesel engines, taking into account the influence of engine parameters, test cycle, fuel types, and after-treatment measures. Compared to conventional diesel, a blend of diesel with 5 % biodiesel resulted in a reduction of the WSII emission factors by 23.7-48.0 %. The emission factors of WSII decreased by 8.4 % after installing selective catalytic reduction (SCR). Dummy variable regression analysis was used to analyze the relationship between WSII and influencing factors. The emission factors of Na+, K+, and Ca2+ were mostly affected by the engine, potentially due to the use of coolants and lubricants containing metal oxides in the engine. The emission factors of NO3- were mainly affected by the test cycle. Techniques for order preference by similarity to ideal solution (TOPSIS) were used to analyze the priority of emission reduction technologies. The results indicated that SCR, biodiesel, and low-sulfur diesel could effectively reduce WSII. This study aims to explore the influence of multiple factors on WSII, providing valuable insights for future research on WSII in DPM.

Untangling microbiota diversity and assembly patterns in the world's longest underground culvert water diversion canal.

The long-distance underground box culvert water transport system (LUBWT) is a crucial link between the source of drinking water and the consumers. It must ensure the stability of water quality during transportation. However, uncontrollable microbial growth can develop in the water delivery system during the long delivery process, posing a risk to health and safety. Therefore, we applied 16 s and 18 s gene sequence analysis in order to study microbial communities in box culvert waters sampled in 2021, as well as a molecular ecological network-based approach to decipher microbial interactions and stability. Our findings revealed that, in contrast to natural freshwater ecosystems, micro-eukaryotes in LUBWT have complex interactions such as predation, parasitism, and symbiosis due to their semi-enclosed box culvert environment. Total nitrogen may be the primary factor affecting bacterial community interactions in addition to temperature. Moreover, employing stability indicators such as robustness and vulnerability, we also found that microbial stability varied significantly from season to season, with summer having the higher stability of microbial communities. Not only that but also the stability of the micronuclei also varied greatly during water transport, which might also be related to the complex interactions among the micro-eukaryotes. To summarize, our study reveals the microbial interactions and stability in LUBWT, providing essential ecological knowledge to ensure the safety of LUBWT's water quality.

Effects of quercetin on granulosa cells from prehierarchical follicles by modulating MAPK signaling pathway in chicken.

Quercetin (Que), widely found in a huge variety of plants, plays important roles in ovarian function. However, to data, there have been no reports about Que regulating granulosa cells (GCs) in prehierarchical follicles in chicken. Herein, GCs from follicles diameter from 4 to 8 mm in chicken were treated by Que in vitro culture to investigate how Que exerts its effect on follicular development. GCs treated by Que in concentrations of 10, 100, and 1,000 ng/mL were tested for cell proliferation and progesterone secretion. Eight cDNA libraries were constructed from GCs (4 samples per group) to explore transcriptome expression changes. The role of the MAPK/ERK signaling pathway was validated in this process. Treatment with 100 and 1,000 ng/mL levels of Que significantly promoted cell proliferation and progesterone secretion (P < 0.05). RNA-seq analysis data showed that 402 and 263 differentially expressed genes (DEGs) were up- and down-regulated, respectively. Functional enrichment analysis that the pathways related to follicular development included biosynthesis of amino acids, MAPK signaling pathway, and calcium signaling pathway. Notably, the function exerted in GCs of the different levels of Que was associated with the suppression of the MAPK pathway. In conclusion, our results proved that low levels of Que could promote MAPK signaling pathway, but high levels of Que inhibit MAPK signaling pathway in GCs from the prehierarchical follicles, promote cell proliferation and progesterone secretion, and benefit follicle selection.

5-alpha reductase inhibitors use in prostatic disease and beyond.

5-alpha reductase inhibitors (5-ARIs) are commonly used and widely available, with benefits observed from their effect on androgen signalling. Their effect relies on the inhibition of the 5-alpha reductase enzyme which aids in the conversion of testosterone to dihydrotestosterone. 5-ARIs have increasing clinical relevance outside of benign prostatic hyperplasia (BPH). Such development requires clinicians to have an updated review to guide clinical practices. This review details the pharmacology and mechanisms of action for 5-ARIs and how this relates to multiple clinical indications. Of note, is the debunked association between finasteride and increased risk of high-grade prostate cancer. Furthermore, adverse effects of 5-ARI use are detailed in this review, with specific mentions to post-finasteride syndrome. In addition to overviews pertaining to BPH and prostate cancer, much attention has also been focused on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The androgen axis may be associated with an increased virulence for SARS-CoV-2 in men, with some reporting a correlation between the severity of illness and androgenic alopecia. Since these observations, the role of antiandrogens, including 5-ARIs, has been explored further in SARS-CoV-2. Increasing understanding of pathological processes involving the androgen axis in which 5-ARIs work, has led to increasing clinical indications for 5-ARIs. Several novel off-label indications have been suggested including its potential role in the pathogenesis of SARS-CoV-2, but to date, these claims have not been substantiated. Previously held truths regarding the role of 5-ARIs and prostate carcinogenesis have been contested, inadvertently leading to the re-exploration of 5-ARIs utility in prostate cancer. With growing evidence into pathological processes involving the androgen axis, 5-ARIs are likely to become increasingly more used. This review serves as a timely update of 5 ARIs pharmacology, current indications and potential future directions.

Novel insight into the underlying dysregulation mechanisms of immune cell-to-cell communication by analyzing multitissue single-cell atlas of two COVID-19 patients.

How does SARS-CoV-2 cause lung microenvironment disturbance and inflammatory storm is still obscure. We here performed the single-cell transcriptome sequencing from lung, blood, and bone marrow of two dead COVID-19 patients and detected the cellular communication among them. Our results demonstrated that SARS-CoV-2 infection increase the frequency of cellular communication between alveolar type I cells (AT1) or alveolar type II cells (AT2) and myeloid cells triggering immune activation and inflammation microenvironment and then induce the disorder of fibroblasts, club, and ciliated cells, which may cause increased pulmonary fibrosis and mucus accumulation. Further study showed that the increase of T cells in the lungs may be mainly recruited by myeloid cells through ligands/receptors (e.g., ANXA1/FPR1, C5AR1/RPS19, and CCL5/CCR1). Interestingly, we also found that certain ligands/receptors (e.g., ANXA1/FPR1, CD74/COPA, CXCLs/CXCRs, ALOX5/ALOX5AP, CCL5/CCR1) are significantly activated and shared among lungs, blood and bone marrow of COVID-19 patients, implying that the dysregulation of ligands/receptors may lead to immune cell's activation, migration, and the inflammatory storm in different tissues of COVID-19 patients. Collectively, our study revealed a possible mechanism by which the disorder of cell communication caused by SARS-CoV-2 infection results in the lung inflammatory microenvironment and systemic immune responses across tissues in COVID-19 patients.

BnaC01.BIN2, a GSK3-like kinase, modulates plant height and yield potential in Brassica napus.

KEY MESSAGE: Using map-based cloning and transgenic transformation, we revealed that glycogen kinase synthase 3-like kinase, BnaC01.BIN2, modulates plant height and yield in rapeseed. The modification of plant height is one of the most important goals in rapeseed breeding. Although several genes that regulate rapeseed plant height have been identified, the genetics mechanisms underlying rapeseed plant height regulation remain poorly understood, and desirable genetic resources for rapeseed ideotype breeding are scarce. Here, we map-based cloned and functionally verified that the rapeseed semi-dominant gene, BnDF4, greatly affects rapeseed plant height. Specifically, BnDF4 encodes brassinosteroid (BR)-insensitive 2, a glycogen synthase kinase 3 primarily expressed in the lower internodes to modulate rapeseed plant height by blocking basal internode-cell elongation. Transcriptome data showed that several cell expansion-related genes involving auxin and BRs pathways were significantly downregulated in the semi-dwarf mutant. Heterozygosity in the BnDF4 allele results in small stature with no marked differences in other agronomic traits. Using BnDF4 in the heterozygous condition, the hybrid displayed strong yield heterosis through optimum intermediate plant height. Our results provide a desirable genetic resource for breeding semi-dwarf rapeseed phenotypes and support an effective strategy for breeding rapeseed hybrid varieties with strong yield heterosis.

The translational landscape of human vascular smooth muscle cells identifies novel short open reading frame-encoded peptide regulators for phenotype alteration.

AIMS: The plasticity of vascular smooth muscle cells (VSMCs) enables them to alter phenotypes under various physiological and pathological stimuli. The alteration of VSMC phenotype is a key step in vascular diseases, including atherosclerosis. Although the transcriptome shift during VSMC phenotype alteration has been intensively investigated, uncovering multiple key regulatory signalling pathways, the translatome dynamics in this cellular process, remain largely unknown. Here, we explored the genome-wide regulation at the translational level of human VSMCs during phenotype alteration. METHODS AND RESULTS: We generated nucleotide-resolution translatome and transcriptome data from human VSMCs undergoing phenotype alteration. Deep sequencing of ribosome-protected fragments (Ribo-seq) revealed alterations in protein synthesis independent of changes in messenger ribonucleicacid levels. Increased translational efficiency of many translational machinery components, including ribosomal proteins, eukaryotic translation elongation factors and initiation factors were observed during the phenotype alteration of VSMCs. In addition, hundreds of candidates for short open reading frame-encoded polypeptides (SEPs), a class of peptides containing 200 amino acids or less, were identified in a combined analysis of translatome and transcriptome data with a high positive rate in validating their coding capability. Three evolutionarily conserved SEPs were further detected endogenously by customized antibodies and suggested to participate in the pathogenesis of atherosclerosis by analysing the transcriptome and single cell RNA-seq data from patient atherosclerotic artery samples. Gain- and loss-of-function studies in human VSMCs and genetically engineered mice showed that these SEPs modulate the alteration of VSMC phenotype through different signalling pathways, including the mitogen-activated protein kinase pathway and p53 pathway. CONCLUSION: Our study indicates that an increase in the capacity of translation, which is attributable to an increased quantity of translational machinery components, mainly controls alterations of VSMC phenotype at the level of translational regulation. In addition, SEPs could function as important regulators in the phenotype alteration of human VSMCs.