PLAU promotes cell proliferation and migration of head and neck cancer via STAT3 signaling pathway.

It was reported that within the head and neck cancer (HNC) cell line CAL21 the epithelial-mesenchymal transition (EMT) and cell proliferation were promoted by Urokinase-Type Plasminogen Activator (PLAU) proteinase through TNFRSF12A. Additionally, in this paper HNC cell lines refer to Fadu and Tu686. A novel PLAU-STAT3 axis was found to be involved in HNC cell line proliferation and metastasis. PLAU expression in HNC samples was upregulated, besides, the elevated expression of PLAU was linked to the lower overall survival (OS) and disease-free survival (DFS). Ectopic PLAU expression promoted cell proliferation and migration, while PLAU knockdown exhibited opposite results. RNA-seq data identified the JAK-STAT signaling pathway, confirmed by western blotting. A recovery assay using S3I-201, a selective inhibitor of signal transducer and activator of transcription 3 (STAT3), indicated that PLAU promoted HNC cell line progression via STAT3 signaling in vitro. The oncogenic role of PLAU in HNC tumor growth in vivo was confirmed using xenograft models. In summary, we identified the tumorigenic PLAU function in the HNC progress. PLAU may represent a potential prognostic biomarker of HNC and the PLAU-STAT3 pathway might be considered a therapeutic target of HNC.

Dynamic genomic changes in methotrexate-resistant human cancer cell lines beyond DHFR amplification suggest potential new targets for preventing drug resistance.

BACKGROUND: Although DHFR gene amplification has long been known as a major mechanism for methotrexate (MTX) resistance in cancer, the early changes and detailed development of the resistance are not yet fully understood. METHODS: We performed genomic, transcriptional and proteomic analyses of human colon cancer cells with sequentially increasing levels of MTX-resistance. RESULTS: The genomic amplification evolved in three phases (pre-amplification, homogenously staining region (HSR) and extrachromosomal DNA (ecDNA)). We confirm that genomic amplification and increased expression of DHFR, with formation of HSRs and especially ecDNAs, is the major driver of resistance. However, DHFR did not play a detectable role in the early phase. In the late phase (ecDNA), increase in FAM151B protein level may also have an important role by decreasing sensitivity to MTX. In addition, although MSH3 and ZFYVE16 may be subject to different posttranscriptional regulations and therefore protein expressions are decreased in ecDNA stages compared to HSR stages, they still play important roles in MTX resistance. CONCLUSION: The study provides a detailed evolutionary trajectory of MTX-resistance and identifies new targets, especially ecDNAs, which could help to prevent drug resistance. It also presents a proof-of-principal approach which could be applied to other cancer drug resistance studies.

Contribution of PGAP3 co-amplified and co-overexpressed with ERBB2 at 17q12 involved poor prognosis in gastric cancer.

The locus at 17q12 erb-b2 receptor tyrosine kinase 2 (ERBB2) has been heavily amplificated and overexpressed in gastric cancer (GC), but it remains to be elucidated about the clinical significance of the co-amplification and co-overexpression of PGAP3 gene located around ERBB2 in GC. The profile of PGAP3 and ERBB2 in four GC cell lines and tissue microarrays containing 418 primary GC tissues was assessed to investigate the co-overexpression and clinical significance of the co-amplified genes, and to evaluate the impact of the co-amplified genes on the malignancy of GC. Co-amplification of PGAP3 and ERBB2 accompanied with co-overexpression was observed in a haploid chromosome 17 of NCI-N87 cells with double minutes (DMs). PGAP3 and ERBB2 were overexpressed and positively correlated in 418 GC patients. Co-overexpression of the PGAP3 and ERBB2 was correlated with T stage, TNM stage, tumour size, intestinal histological type and poor survival proportion in 141 GC patients. In vitro, knockdown of the endogenous PGAP3 or ERBB2 decreased cell proliferation and invasion, increased G1 phase accumulation and induced apoptosis in NCI-N87 cells. Furthermore, combined silencing of PGAP3 and ERBB2 showed an additive effect on resisting proliferation of NCI-N87 cells compared with targeting ERBB2 or PGAP3 alone. Taken together, the co-overexpression of PGAP3 and ERBB2 may be crucial due to its significant correlation with clinicopathological factors of GC. Haploid gain of PGAP3 co-amplified with ERBB2 is sufficient to facilitate the malignancy and progression of GC cells in a synergistic way.

Fruit and Vegetable Consumption and the Risk of Prostate Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Emerging researches has evaluated whether fruit and vegetable consumption reduce the risk of prostate cancer. However, the conclusions of published articles remained confusing. Thus, we conducted an updated systematic review and meta-analysis to confirm the relationship of fruit and vegetable consumption and the risk of prostate cancer. METHOD: We searched PubMed, EMBASE, Web of Science and Chinese National Knowledge Infrastructure (CNKI) up to September 1, 2020. We finally included 17 cohort studies related to fruit or vegetable intake after rigid quality assessment and checking references of the retrieved articles and relevant reviews. Newcastle-Ottawa scale was adopted to assess the quality of studies and random effect model with RR and 95% CI were used to assess the risk. RESULTS: No significant relationship was found between fruit consumption (RR = 1.00, 95% CI = 0.94-1.05) and vegetable consumption (RR = 0.98, 95% CI = 0.94-1.02) and the risk of prostate cancer. No significant heterogeneity or publication bias was identified. CONCLUSION: Our updated meta-analysis demonstrated that fruit and vegetable consumption can barely reduce the risk of prostate cancer with several limitations. Further clinical and basic researches are eagerly awaited to confirm our results and clarify the potential biological mechanisms.

Genome-Wide Characterization of Trehalose-6-Phosphate Synthase Gene Family of Brassica napus and Potential Links with Agronomic Traits.

Trehalose and trehalose-6 phosphate played important roles in floral organ development, embryonic development, cell morphogenesis, and signal transduction under abiotic stress. However, little is known about the trehalose-6-phosphate synthase (TPS) gene family in Brassica napus. In this study, in total, 26 TPS genes in B. napus (BnTPS genes) were identified and classified into two groups. In each group, the BnTPS genes showed relatively conserved gene structures. The protein-protein interaction (PPI) network and enrichment analysis indicated that BnTPS genes were involved in the glycolysis/gluconeogenesis, fructose and mannose metabolism, galactose metabolism, pentose phosphate pathway, carbohydrate transmembrane transport, trehalose-phosphatase activity, etc. The expression of BnTPS genes varied greatly across different tissues, while most of the BnTPS genes showed a considerable improvement in expression under different abiotic stresses, indicating that BnTPS genes were significantly responsive to the abiotic treatments. In addition, the association mapping analysis revealed that eight BnTPS genes were potential regulators of particular agronomic traits. Among them, the gene BnTPS23 was significantly associated with the primary flowering time (PFT), full flowering time (FFT1), and final flowering time (FFT2), suggesting that BnTPS genes may play an important role in regulating key agronomic traits in B. napus. In summary, our research provides a better understanding of BnTPS genes, facilitates the breeding of superior B. napus varieties, and paves the way for future functional studies.

ZIP4 Increases Expression of Transcription Factor ZEB1 to Promote Integrin α3ß1 Signaling and Inhibit Expression of the Gemcitabine Transporter ENT1 in Pancreatic Cancer Cells.

BACKGROUND & AIMS: Pancreatic tumors undergo rapid growth and progression, become resistant to chemotherapy, and recur after surgery. We studied the functions of the solute carrier family 39 member 4 (SLC39A4, also called ZIP4), which regulates concentrations of intracellular zinc and is increased in pancreatic cancer cells, in cell lines and mice. METHODS: We obtained 93 pancreatic cancer specimens (tumor and adjacent nontumor tissues) from patients who underwent surgery and gemcitabine chemotherapy and analyzed them by immunohistochemistry. ZIP4 and/or ITGA3 or ITGB1 were overexpressed or knocked down with short hairpin RNAs in AsPC-1 and MIA PaCa-2 pancreatic cancer cells lines, and in pancreatic cells from KPC and KPC-ZEB1-knockout mice, and pancreatic spheroids were established; cells and spheroids were analyzed by immunoblots, reverse transcription polymerase chain reaction, and liquid chromatography tandem mass spectrometry. We studied transcriptional regulation of ZEB1, ITGA3, ITGB1, JNK, and ENT1 by ZIP4 using chromatin precipitation and luciferase reporter assays. Nude mice were given injections of genetically manipulated AsPC-1 and MIA PaCa-2 cells, and growth of xenograft tumors and metastases was measured. RESULTS: In pancreatic cancer specimens from patients, increased levels of ZIP4 were associated with shorter survival times. MIA PaCa-2 cells that overexpressed ZIP4 had increased resistance to gemcitabine, 5-fluorouracil, and cisplatin, whereas AsPC-1 cells with ZIP4 knockdown had increased sensitivity to these drugs. In mice, xenograft tumors grown from AsPC-1 cells with ZIP4 knockdown were smaller and more sensitive to gemcitabine. ZIP4 overexpression significantly reduced accumulation of gemcitabine in pancreatic cancer cells, increased growth of xenograft tumors in mice, and increased expression of the integrin subunits ITGA3 and ITGB1; expression levels of ITGA3 and ITGB1 were reduced in cells with ZIP4 knockdown. Pancreatic cancer cells with ITGA3 or ITGB1 knockdown had reduced proliferation and formed smaller tumors in mice, despite overexpression of ZIP4; spheroids established from these cells had increased sensitivity to gemcitabine. We found ZIP4 to activate STAT3 to induce expression of ZEB1, which induced expression of ITGA3 and ITGB1 in KPC cells. Increased ITGA3 and ITGB1 expression and subsequent integrin α3ß1 signaling, via c-Jun-N-terminal kinase (JNK), inhibited expression of the gemcitabine transporter ENT1, which reduced gemcitabine uptake by pancreatic cancer cells. ZEB1-knockdown cells had increased sensitivity to gemcitabine. CONCLUSIONS: In studies of pancreatic cancer cell lines and mice, we found that ZIP4 increases expression of the transcription factor ZEB1, which activates expression of ITGA3 and ITGB1. The subsequent increase in integrin α3ß1 signaling, via JNK, inhibits expression of the gemcitabine transporter ENT1, so that cells take up smaller amounts of the drug. Activation of this pathway might help mediate resistance of pancreatic tumors to chemotherapeutic agents.

LncRNA FGF14-AS2 represses growth of prostate carcinoma cells via modulating miR-96-5p/AJAP1 axis.

OBJECTIVE: This investigation devoted to lncRNA FGF14 antisense RNA 2 (FGF14-AS2) in prostate carcinoma progression. METHODS: The levels of lncRNA FGF14-AS2, miR-96-5p, and Adherens junction-associated protein-1 (AJAP1) in prostate carcinoma were tested by Western blot and qRT-PCR. How these two genes interacted was confirmed by RNA immunoprecipitation and dualluciferase gene methods. The effect of FGF14-AS2/miR-96-5p/AJAP1 axis in prostate carcinoma progression was determined by MTT, Transwell, and nude mice tumor model. RESULTS: FGF14-AS2 was a downregulated lncRNA in prostate carcinoma tissue and cells. FGF14-AS2 could restrain miR-96-5p expression while miR-96-5p hampered AJAP1. FGF14-AS2 could effectively decrease the biological behaviors of prostate carcinoma cells, while knock-down of FGF14-AS2 triggered opposite results. Moreover, miR-96-5p mimic presented a cancer promoter role in prostate carcinoma cells. AJAP1 expression level could affect levels of proteins related to epithelial-mesenchymal transition. In vivo experiment suggested that overexpressing FGF14-AS2 could reverse the promotion of silenced AJAP1 on prostate carcinoma cell metastasis, thus to inhibit tumor growth. CONCLUSION: lncRNA FGF14-AS2 was a downregulated lncRNA in prostate carcinoma and influenced cell proliferation and metastasis. The influence relied on modulating miR-96-5p and its target gene AJAP1.

Molecular structure and evolution mechanism of two populations of double minutes in human colorectal cancer cells.

Gene amplification chiefly manifests as homogeneously stained regions (HSRs) or double minutes (DMs) in cytogenetically and extrachromosomal DNA (ecDNA) in molecular genetics. Evidence suggests that gene amplification is becoming a hotspot for cancer research, which may be a new treatment strategy for cancer. DMs usually carry oncogenes or chemoresistant genes that are associated with cancer progression, occurrence and prognosis. Defining the molecular structure of DMs will facilitate understanding of the molecular mechanism of tumorigenesis. In this study, we re-identified the origin and integral sequence of DMs in human colorectal adenocarcinoma cell line NCI-H716 by genetic mapping and sequencing strategy, employing high-resolution array-based comparative genomic hybridization, high-throughput sequencing, multiplex-fluorescence in situ hybridization and chromosome walking techniques. We identified two distinct populations of DMs in NCI-H716, confirming their heterogeneity in cancer cells, and managed to construct their molecular structure, which were not investigated before. Research evidence of amplicons distribution in two different populations of DMs suggested that a multi-step evolutionary model could fit the module of DM genesis better in NCI-H716 cell line. In conclusion, our data implicated that DMs play a very important role in cancer progression and further investigation is necessary to uncover the role of the DMs.

ZIP4 Promotes Muscle Wasting and Cachexia in Mice With Orthotopic Pancreatic Tumors by Stimulating RAB27B-Regulated Release of Extracellular Vesicles From Cancer Cells.

BACKGROUND & AIMS: Cachexia, which includes muscle wasting, is a frequent complication of pancreatic cancer. There are no therapies that reduce cachexia and increase patient survival, so it is important to learn more about its mechanisms. The zinc transporter ZIP4 promotes growth and metastasis of pancreatic tumors. We investigated its effects on muscle catabolism via extracellular vesicle (EV)-mediated stimulation of mitogen-activated protein kinase 14 (p38 MAPK). METHODS: We studied nude mice with orthotopic tumors grown from human pancreatic cancer cell lines (AsPC-1 and BxPC-3); tumors were removed 8 days after cell injection and analyzed by histology. Mouse survival was analyzed by Kaplan-Meier curves. ZIP4 was knocked down in AsPC-1 and BxPC-3 cells with small hairpin RNAs; cells with empty vectors were used as controls. Muscle tissues were collected from mice and analyzed by histology and immunohistochemistry. Conditioned media from cell lines and 3-dimensional spheroid/organoid cultures of cancer cells were applied to C2C12 myotubes. The myotubes and the media were analyzed by immunoblots, enzyme-linked immunosorbent assays, and immunofluorescence microscopy. EVs were isolated from conditioned media and analyzed by immunoblots. RESULTS: Mice with orthotopic tumors grown from pancreatic cancer cells with knockdown of ZIP4 survived longer and lost less body weight and muscle mass than mice with control tumors. Conditioned media from cancer cells activated p38 MAPK, induced expression of F-box protein 32 and UBR2 in C2C12 myotubes, and also led to loss of myofibrillar protein myosin heavy chain and myotube thinning. Knockdown of ZIP4 in cancer cells reduced these effects. ZIP4 knockdown also reduced pancreatic cancer cell release of heat shock protein (HSP) 70 and HSP90, which are associated with EVs, by decreasing CREB-regulated expression of RAB27B. CONCLUSIONS: ZIP4 promotes growth of orthotopic pancreatic tumors in mice and loss of muscle mass by activating CREB-regulated expression of RAB27B, required for release of EVs from pancreatic cancer cells. These EVs activate p38 MAPK and induce expression of F-box protein 32 and UBR2 in myotubes, leading to loss of myofibrillar myosin heavy chain and myotube thinning. Strategies to disrupt these pathways might be developed to reduce pancreatic cancer progression and accompanying cachexia.

Recursive Paleohexaploidization Shaped the Durian Genome.

The durian (Durio zibethinus) genome has recently become available, and analysis of this genome reveals two paleopolyploidization events previously inferred as shared with cotton (Gossypium spp.). Here, we reanalyzed the durian genome in comparison with other well-characterized genomes. We found that durian and cotton were actually affected by different polyploidization events: hexaploidization in durian ∼19-21 million years ago (mya) and decaploidization in cotton ∼13-14 mya. Previous interpretations of shared polyploidization events may have resulted from the elevated evolutionary rates in cotton genes due to the decaploidization and insufficient consideration of the complexity of plant genomes. The decaploidization elevated evolutionary rates of cotton genes by ∼64% compared to durian and explained a previous ∼4-fold over dating of the event. In contrast, the hexaploidization in durian did not prominently elevate gene evolutionary rates, likely due to its long generation time. Moreover, divergent evolutionary rates probably explain 98.4% of reconstructed phylogenetic trees of homologous genes being incongruent with expected topology. The findings provide further insight into the roles played by polypoidization in the evolution of genomes and genes, and they suggest revisiting existing reconstructed phylogenetic trees.

An epidemiological survey of laryngopharyngeal reflux disease at the otorhinolaryngology-head and neck surgery clinics in China.

PURPOSE: Using the Reflux Symptom Index (RSI), this nationwide study aimed to investigate the incidence, diagnostic status, risk factors, and common symptoms of adult laryngopharyngeal reflux disease (LPRD) at otorhinolaryngology-head and neck surgery (OHNS) clinics in China. METHODS: This multicenter cross-sectional survey began at the different institutions ranged from July to October 2017, and the duration was 12 months. A total of 90,440 eligible patients were finally enrolled from 72 medical institutions in China. All these patients completed the questionnaire based on RSI. In this study, LPRD was defined as RSI > 13. RESULTS: There were 9182 with LPRD among the 90,440 eligible participants (10.15%). However, only 1294 had a history of LPRD diagnosis among those with LPRD (14.09%). There were regional differences in the frequency of LPRD (P < 0.001). The proportions of patients with LPRD in males (vs. females), middle- and old-aged patients (vs. young), with current smoking history (vs. no smoking), and current drinking history (vs. no drinking) were significantly higher (all P < 0.001). Middle and old age, current smoking, and drinking history were independent predictors of LPRD (all P < 0.001, OR 1.240, 1.261, and 1.481, respectively). "Sensations of something stuck in throat or a lump in throat", "clearing throat", and "excess throat mucus or postnasal drip" were the most frequent clinical symptoms in patients with LPRD. CONCLUSIONS: LPRD has a high incidence at the OHNS clinics in China. However, the diagnostic status of this disease is not optimistic. Older age, smoking, and drinking history were risk factors for LPRD.

Inhibiting homologous recombination decreases extrachromosomal amplification but has no effect on intrachromosomal amplification in methotrexate-resistant colon cancer cells.

Gene amplification, which involves the two major topographical structures double minutes (DMs) and homegeneously stained region (HSR), is a common mechanism of treatment resistance in cancer and is initiated by DNA double-strand breaks. NHEJ, one of DSB repair pathways, is involved in gene amplification as we demonstrated previously. However, the involvement of homologous recombination, another DSB repair pathway, in gene amplification remains to be explored. To better understand the association between HR and gene amplification, we detected HR activity in DM- and HSR-containing MTX-resistant HT-29 colon cancer cells. In DM-containing MTX-resistant cells, we found increased homologous recombination activity compared with that in MTX-sensitive cells. Therefore, we suppressed HR activity by silencing BRCA1, the key player in the HR pathway. The attenuation of HR activity decreased the numbers of DMs and DM-form amplified gene copies and increased the exclusion of micronuclei and nuclear buds that contained DM-form amplification; these changes were accompanied by cell cycle acceleration and increased MTX sensitivity. In contrast, BRCA1 silencing did not influence the number of amplified genes and MTX sensitivity in HSR-containing MTX-resistant cells. In conclusion, our results suggest that the HR pathway plays different roles in extrachromosomal and intrachromosomal gene amplification and may be a new target to improve chemotherapeutic outcome by decreasing extrachromosomal amplification in cancer.

An Overlooked Paleotetraploidization in Cucurbitaceae.

Cucurbitaceae plants are of considerable biological and economic importance, and genomes of cucumber, watermelon, and melon have been sequenced. However, a comparative genomics exploration of their genome structures and evolution has not been available. Here, we aimed at performing a hierarchical inference of genomic homology resulted from recursive paleopolyploidizations. Unexpectedly, we found that, shortly after a core-eudicot-common hexaploidy, a cucurbit-common tetraploidization (CCT) occurred, overlooked by previous reports. Moreover, we characterized gene loss (and retention) after these respective events, which were significantly unbalanced between inferred subgenomes, and between plants after their split. The inference of a dominant subgenome and a sensitive one suggested an allotetraploid nature of the CCT. Besides, we found divergent evolutionary rates among cucurbits, and after doing rate correction, we dated the CCT to be 90-102 Ma, likely common to all Cucurbitaceae plants, showing its important role in the establishment of the plant family.

Public mobilisation in implementation of smoke-free Beijing: a social media complaint platform.

In November 2014, Beijing People's Congress adopted the Beijing Smoking Control Ordinance and a key provision bans smoking in all indoor public places, workplaces and on public transport. To ensure effective implementation of the ordinance, the government calls on the whole society to take part. In response, Beijing Tobacco Control Association, with the support of a local technology company, developed the Beijing Tobacco Control Map, a digital system that enables comprehensive tobacco control information collection, data visualisation and mapping. A key component of the Beijing Tobacco Control Map is the Complaint Map which is generated by the data of reported violations of the smoke-free provisions by the general public through a social media platform. The Complaint Map visually displays the reported violations on a map of Beijing in real time. The general public can access the Complaint Map at any time to see which venues and locations have been reported. It is used by tobacco control volunteers, who are recruited and trained to address complaints and promote compliance. It is also used by the government's enforcement team for targeted inspections. The Complaint Map has effectively engaged the public and promoted a smoke-free Beijing. Beijing's innovative and systematic approach that involves the Complaint Map, volunteer management, coordination with the enforcement team, and media exposure can be replicated or adapted in other cities in China and abroad that are implementing smoke-free laws or tobacco control laws in general.

Genomic, expressional, protein-protein interactional analysis of Trihelix transcription factor genes in Setaria italia and inference of their evolutionary trajectory.

BACKGROUND: Trihelix transcription factors (TTF) play important roles in plant growth and response to adversity stress. Until now, genome-wide identification and analysis of this gene family in foxtail millet has not been available. Here, we identified TTF genes in the foxtail millet and its grass relatives, and characterized their functional domains. RESULTS: As to sequence divergence, TTF genes were previously divided into five subfamilies, I-V. We found that Trihelix family members in foxtail millet and other grasses mostly preserved their ancestral chromosomal locations during millions of years' evolution. Six amino acid sites of the SIP1 subfamily possibly were likely subjected to significant positive selection. Highest expression level was observed in the spica, with the SIP1 subfamily having highest expression level. As to the origination and expansion of the gene family, notably we showed that a subgroup of subfamily IV was the oldest, and therefore was separated to define a new subfamily O. Overtime, starting from the subfamily O, certain genes evolved to form subfamilies III and I, and later from subfamily I to develop subfamilies II and V. The oldest gene, Si1g016284, has the most structural changes, and a high expression in different tissues. What's more interesting is that it may have bridge the interaction with different proteins. CONCLUSIONS: By performing phylogenetic analysis using non-plant species, notably we showed that a subgroup of subfamily IV was the oldest, and therefore was separated to define a new subfamily O. Starting from the subfamily O, certain genes evolved to form other subfamilies. Our work will contribute to understanding the structural and functional innovation of Trihelix transcription factor, and the evolutionary trajectory.

Screening of Bioactive Ingredients in Ligusticum Chuanxiong Hort for Protection against Myocardial Ischemia.

BACKGROUND/AIMS: To study the spectrum-effect relationship and effective components of Ligusticum Chuanxiong Hort. (LCH) on the protection of canine myocardial ischemia. METHODS: Fingerprint spectrum of LCH extracts was developed using high performance liquid chromatography (HPLC), and a canine model of acute myocardial ischemia was established by ligating the coronary artery. Bivariate correlation analysis and multivariate regression analysis were used to correlate the pharmacodynamics of LCH extract and its common peaks in HPLC. RESULTS: The bioactive components of LCH were ligustrazine, ferulic acid, cnidilide and ligustilide. Ligustrazine and ferulic acid could significantly reduce serum lactic acid in canine model of acute myocardial ischemia, while ligustilide could significantly reduce the elevation of serum free fatty acid. CONCLUSIONS: The spectrum-effect relationship study shows that the effective components of LCH are ligustrazine, ferulic acid, cnidilide and ligustilide, which have protective effect on myocardial ischemia.

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

The prognostic and immunological role of MYB: from bladder cancer validation to pan-cancer analysis.

BACKGROUND: MYB proto-oncogene is verified as a transcription factor. Although emerging evidence showed that MYB plays a critical part in tumor progression and immunity, a systematic pan-cancer analysis of MYB still remains to be performed for determining whether MYB could serve as a biomarker for cancer screening, prognosis prediction and accurate therapy design in various human cancers. METHODS: In the present study, we performed qRT-PCR, wound healing assay and transwell assay to validate the expression level and biological function of MYB in bladder cancer. Then, we utilized several open-source databases including UCSC Xena database, TCGA, GTEx, etc. Online tools was used to process the raw data from UCSC Xena database. RESULTS: We found that the expression level of MYB is significantly higher in bladder cancer cell lines than urothelial cells. Further experiments confirmed that overexpression of MYB enhanced the ability of migration in bladder cancer. Next, we found that the expression level of MYB is significantly higher in most cancers. Meanwhile, MYB expression was positively or negatively related with the prognosis in different cancer types. In addition, MYB expression is significantly related to immune score and immune cells in most cancer types. Moreover, MYB act as an immunotherapy biomarker superior to several traditional immunotherapy biomarkers. Finally, deep deletion was the most frequent genetic alteration of MYB. CONCLUSION: MYB may serve as a powerful biomarker for tumor screening, prognostic, individualized treatment strategy in a broad range of malignancies.

Novel quantitative trait loci from an interspecific Brassica rapa derivative improve pod shatter resistance in Brassica napus.

Pod shatter is a trait of agricultural relevance that ensures plants dehisce seeds in their native environment and has been subjected to domestication and selection for non-shattering types in several broadacre crops. However, pod shattering causes a significant yield reduction in canola (Brassica napus L.) crops. An interspecific breeding line BC95042 derived from a B. rapa/B. napus cross showed improved pod shatter resistance (up to 12-fold than a shatter-prone B. napus variety). To uncover the genetic basis and improve pod shatter resistance in new varieties, we analysed F2 and F2:3 derived populations from the cross between BC95042 and an advanced breeding line, BC95041, and genotyped with 15,498 DArTseq markers. Through genome scan, interval and inclusive composite interval mapping analyses, we identified seven quantitative trait loci (QTLs) associated with pod rupture energy, a measure for pod shatter resistance or pod strength, and they locate on A02, A03, A05, A09 and C01 chromosomes. Both parental lines contributed alleles for pod shatter resistance. We identified five pairs of significant epistatic QTLs for additive x additive, additive dominance and dominance x dominance interactions between A01/C01, A03/A07, A07/C03, A03/C03, and C01/C02 chromosomes for rupture energy. QTL effects on A03/A07 and A01/C01 were in the repulsion phase. Comparative mapping identified several candidate genes (AG, ABI3, ARF3, BP1, CEL6, FIL, FUL, GA2OX2, IND, LATE, LEUNIG, MAGL15, RPL, QRT2, RGA, SPT and TCP10) underlying main QTL and epistatic QTL interactions for pod shatter resistance. Three QTLs detected on A02, A03, and A09 were near the FUL (FRUITFULL) homologues BnaA03g39820D and BnaA09g05500D. Focusing on the FUL, we investigated putative motifs, sequence variants and the evolutionary rate of its homologues in 373 resequenced B. napus accessions of interest. BnaA09g05500D is subjected to purifying selection as it had a low Ka/Ks ratio compared to other FUL homologues in B. napus. This study provides a valuable resource for genetic improvement for yield through an understanding of the genetic mechanism controlling pod shatter resistance in Brassica species.