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Severe Acute Respiratory Syndrome (SARS) not only paralysed economic activities in SARS-affected cities, it also affected sporting activities. SARS was identified in Hong Kong in late February 2003 and the WHO issued a global alert on 12 March, 2003. The incubation period of SARS is usually 4-6 days and patients commonly present with high fever (temperature >38°C), dry cough, chills and rigor, dyspnoea and diarrhoea. Although a specific antiviral agent and vaccines for SARS are not available at the time of writing, a standard treatment protocol for SARS has been developed. The average mortality rate is about 16% in Hong Kong. The coronavirus is a common pathogen for upper respiratory tract infection and is the most probable pathogen for SARS. Transmission methods may, therefore, be similar for both these infections. Transmission is possible when aerosolised viral particles come into contact with the susceptible host's mucous membrane, most commonly the nose, but also the mouth and eyes. With appropriate preventive measures to avoid contact with virus, the probability of infection is minimal. Isolation of those who have had close contact with confirmed or suspected SARS patients and/or who have persistent fever will be the most effective and practical method of avoiding contact. Maintaining personal hygiene and frequent hand washing can also reduce the risk of infection. Using diluted bleach (1 part bleach in 99 parts water) to cleanse training areas and equipment is also recommended. With proper event planning to conform with quarantine measures, special travel arrangements, facility sterilisation and use of venues with good ventilation and filtering systems, sport competition can still proceed. [ABSTRACT FROM AUTHOR]

Pollination syndromes are a key component of flowering plant diversification, prompting questions about the architecture of single traits and genetic coordination among traits. Here, we investigate the genetics of extreme floral divergence between naturally hybridizing monkeyflowers, Mimulus parishii (self-pollinated) and M. cardinalis (hummingbird-pollinated). We mapped quantitative trait loci (QTLs) for 18 pigment, pollinator reward/handling, and dimensional traits in parallel sets of F 2 hybrids plus recombinant inbred lines and generated nearly isogenic lines (NILs) for two dimensional traits, pistil length and corolla size. Our multi-population approach revealed a highly polygenic basis (n = 190 QTLs total) for pollination syndrome divergence, capturing minor QTLs even for pigment traits with leading major loci. There was significant QTL overlap within pigment and dimensional categories. Nectar volume QTLs clustered with those for floral dimensions, suggesting a partially shared module. The NILs refined two pistil length QTLs, only one of which has tightly correlated effects on other dimensional traits. An overall polygenic architecture of floral divergence is partially coordinated by genetic modules formed by linkage (pigments) and likely pleiotropy (dimensions plus nectar). This work illuminates pollinator syndrome diversification in a model radiation and generates a robust framework for molecular and ecological genomics., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)

Ectomycorrhizal fungi (EMF) play pivotal roles in determining temperate forest ecosystem processes. We tracked root EMF community succession across saplings, juveniles, and adults of three temperate broadleaf trees (Acer mono, Betula platyphylla, and Quercus mongolica) in Northeast China. Adult stages showed higher alpha diversity but lower community dissimilarity compared to earlier stages. In particular, the EMF alpha diversity of Quercus mongolica marginally increased along with host developmental stages and ranked as sapling < juvenile < adult. Unlike those of Acer mono and Quercus mongolica, the EMF community composition of Betula platyphylla showed greater variation between the sapling and juvenile stages than between the sapling and adult stages. Cooccurrence networks revealed increasing interconnectivity with host maturity, dominated by positive correlations (> 99%). LEfSe was employed to identify stage- and/or host-specific EMF indicators. This study highlighted the assembly of EMF community during the development of broadleaf trees in temperate forests, thereby advancing understanding of the succession and coevolution of symbiotic relationships., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

While RNA silencing is crucial for plant resistance against viruses, the cellular connections between RNA silencing and antiviral responses in plants remain poorly understood. In this study, we aim to investigate this relationship by examining the subcellular localization of small RNA loading and viral replication in Arabidopsis. Our findings reveal that Argonaute 2 (AGO2), a key component of RNA silencing, loads small RNAs at the endoplasmic reticulum (ER)-chloroplast membrane contact sites (MCSs). We identify a chloroplast-localized protein, RNA helicase 3 (RH3), which interacts with AGO2 and facilitates the loading of small RNAs into AGO2 at these MCSs. Furthermore, we discover that MCSs serve as replication sites for certain plant viruses. RH3 also promotes the loading of viral-derived small RNAs into AGO2, thereby enhancing plant antiviral resistance. Overall, our study sheds light on the roles of RH3 in RNA silencing and plant antiviral defenses, providing valuable insights into the cytobiological connections between RNA silencing, viral replication, and antiviral immunity., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Aims: To investigate the role of transcription factor activating enhancer-binding protein 4 (TFAP4) in gastric cancer (GC) progression and elucidate its mechanism in promoting metastasis and invasion through the PI3K/AKT signaling pathway., Methods: Bioinformatics analysis was performed to assess TFAP4 expression in GC tissues. Clinical specimens were collected and validated for TFAP4 expression. Functional assays were conducted to evaluate the effects of TFAP4 overexpression and inhibition on GC cell proliferation, invasion, and metastasis. In vivo studies with HGC27 cells in BALB/c nude mice were used to assess tumor growth and metastasis. Mechanistic analysis included the measurement of MCM5 expression and activation of the PI3K/AKT signaling pathway, with PI3K inhibitor LY294002 and MCM5 knockdown applied to confirm the pathways involved., Results: Elevated TFAP4 expression was observed in GC tissues, and its overexpression promoted GC cell proliferation, invasion, and metastasis. Conversely, TFAP4 inhibition suppressed these behaviors. In vivo studies confirmed that TFAP4 knockdown reduced tumor growth and metastasis in nude mice. Mechanistically, TFAP4 was found to activate MCM5, which in turn facilitated GC cell invasion and metastasis. Furthermore, TFAP4 and MCM5 activated the PI3K/AKT signaling pathway, as evidenced by increased p-PI3K and p-AKT expression. The effects of TFAP4 overexpression were reversed by MCM5 knockdown or treatment with the PI3K inhibitor LY294002., Conclusion: The TFAP4-MCM5 signaling axis promotes GC progression through the PI3K/AKT pathway, suggesting that targeting this axis could provide a potential therapeutic strategy for managing gastric cancer., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflicts of interest. Ethics approval and consent to participate: This study was approved by the Institutional Ethics Committee of Second Affiliated Hospital of Nanchang University (Review [2020] No. 058). All procedures performed in this study using human data were in accordance with the Declaration of Helsinki (as revised in 2013). Informed consent was waived by the Institutional Ethics Committee of Second Affiliated Hospital of Nanchang University because of the retrospective nature of this study. All animal experiments were carried out in accordance with the “Guidelines for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee of Nanchang Royo Biotech Co. Ltd (RYE2023080701). Consent for publication: All authors agree to the publication of this article., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Partially replacing NaCl with KCl under ultrasound can improve muscle quality and reduce oxidative degeneration of myofibrillar proteins in semi-dried large yellow croaker (Larimichthys crocea). Myosin, the most important protein in myofibrillar protein, plays an important role in muscle quality. Hence, the present study aimed to investigate the effect of replacing NaCl with KCl on the physicochemical properties of myosin derived from large yellow croaker under ultrasound. Furthermore, the application potential of ultrasound to low sodium salt products was evaluated., Results: The results showed that ultrasound treatment reduced the aggregation and particle size of myosin. By contrast, at high salt concentrations, myosin oxidation was inhibited and protein aggregation increased. This led to an increase in particle size and a decrease in stability and surface hydrophobicity of myosin. Interestingly, KCl increased myosin solubility and promoted protein unfolding, the excess of which exposed some active sites, leading to oxidative destruction of the proteins. In the present study, the chromophore and surface hydrophobic groups of myosin were exposed as a result of the KCl-mediated unfolding of the α-helices of myosin after the partial replacement of NaCl with KCl. This improved the structural stability of myosin and reduced its oxidative damage., Conclusion: The findings of the present study show that the presence of NaCl and KCl in the system was more conducive to protecting the key role of myosin in the muscle tissue compared with NaCl alone. Additionally, the study provides insights into the mechanism of K + and Na + action on myosin under ultrasound, along with a theoretical basis for the application of ultrasound in low sodium salt products. © 2025 Society of Chemical Industry., (© 2025 Society of Chemical Industry.)

Enhancing the transcriptional activation activity of transcription factors (TFs) has multiple applications in organism improvement, metabolic engineering, and other aspects of plant science, but the approaches remain unclear. Here, we used gene activation assays and genetic transformation to investigate the transcriptional activities of two MYB TFs, PRODUCTION OF ANTHOCYANIN PIGMENT 1 (AtPAP1) from Arabidopsis (Arabidopsis thaliana) and EsMYBA1 from Epimedium (Epimedium sagittatum), and their synthetic variants in a range of plant species from several families. Using anthocyanin biosynthesis as a convenient readout, we discovered that homologous naturally occurring TFs showed differences in the transcriptional activation ability and that similar TFs induced large changes in the genetic program when heterologously expressed in different species. In some cases, shuffling the DNA-binding domains and transcriptional activation domains (ADs) between homologous TFs led to synthetic TFs that had stronger activation potency than the original TFs. More importantly, synthetic TFs derived from MYB, NAC, bHLH, and ethylene-insensitive3-like (EIL) family members containing tandemly repeated ADs had greatly enhanced activity compared to their natural counterparts. These findings enhance our understanding of TF activity and demonstrate that employing tandemly repeated ADs from natural TFs is a simple and widely applicable strategy to enhance the activation potency of synthetic TFs., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Leaf senescence is a complex process that is triggered by many developmental and environmental factors. However, the mechanisms regulating leaf senescence remain unclear. Here, we revealed that rice ribulose-1,5-bisphosphate carboxylase/oxygenase activase (RCA) promotes the onset of basal dark-induced senescence. RCA was mainly expressed in the leaves, and its expression level quickly declined under dark conditions. Furthermore, rca mutant plants presented a prolonged leaf longevity phenotype in the dark, whereas overexpression of the large isoform of RCA (RCA L ), not small isoform (RCA S ), in rice and Arabidopsis accelerated leaf senescence. Filamentation temperature-sensitive H (OsFtsH1), a zinc metalloprotease, interacts with RCA L and RCA S and presents a higher binding efficiency to RCA L than RCA S in darkness. Furthermore, we found that RCA L promotes 26S proteasome-mediated degradation of OsFtsH1 protein, which can be inhibited by protease inhibitor MG132. Consequently, OsFtsH1 loss-of-function mutants exhibit accelerated leaf senescence, whereas OsFtsH1-overexpressing plants display delayed senescence. Collectively, our findings highlight the significant role of RCA L isoform in regulating leaf senescence under dark conditions, particularly through enhancing the degradation of OsFtsH1., (© 2025 Society for Experimental Biology and John Wiley & Sons Ltd.)

Large yellow croaker (Larimichthys crocea) is susceptible to oxidative denaturation during storage. This work is to investigate the quality alterations by analyzing its physicochemical changes and proteomics throughout preservation under refrigeration, frozen, and slurry ice (SI) conditions. Results revealed that the freshness of large yellow croaker, as evaluated by indicators such as total volatile basic nitrogen, total viable count, and thiobarbituric acid reactive substances, was well maintained while stored in the SI group. Meanwhile, the water distribution in the muscle tissue of group SI exhibited slower fluctuations, thereby preserving the integrity of fish muscle cells. Based on label-free proteomic analysis, a considerable downregulation was observed in the mitogen-activated protein kinase (MAPK) signaling pathway, indicating that SI decelerated this metabolic pathway and effectively delayed the deterioration of muscle. Therefore, the application of SI provides potential for maintaining the quality stability of large yellow croaker., Competing Interests: Declaration of competing interest The authors declare that they do not possess any recognized competing financial interests or personal relationships that could have potentially influenced the findings presented in this research., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The reaction-diffusion (RD) system is widely assumed to account for many complex, self-organized pigmentation patterns in natural organisms. However, the specific configurations of such RD networks and how RD systems interact with positional information (i.e., prepatterns) that may specify the initiation conditions for the RD operation remain largely unknown. Here, we introduced a three-substance RD system underlying the formation of repetitive pigment spots and stripes in Mimulus flowers. It consists of an R2R3-MYB activator (NEGAN), an R3-MYB inhibitor (RTO), and a coactivator represented by two paralogous bHLH proteins. Through fine-scale genetic analyses, transgenic experiments, and computer simulations, we identified the causal loci contributing to the evolutionary transition from sparsely dispersed spots to longitudinal stripes. Genetic changes at these loci modulate the prepatterns of the activator and coactivator expression and the promoter activities of the inhibitor and one of the coactivator paralogs. Our findings highlight the importance of prepatterns towards a realistic description of RD systems in natural organisms, and reveal the genetic mechanism generating pattern variation through modulation of the kinetics of the RD system and its prepatterns., Competing Interests: Declaration of competing interests The authors declare no competing interests.

Objective: Vascular hyporeactivity increases with the incidence of obstructive jaundice (OJ). Evidence suggests that OJ activates the farnesoid X receptor (FXR) as well as the large-conductance Ca 2+ -activated K + (BK Ca or MaxiK) channel. This study was designed to explore the role of the FXR in vascular hyporesponsiveness induced by cholestasis., Methods: The OJ model rats were constructed by bile duct ligation (BDL) and treated with an FXR agonist or antagonist. Vasoconstriction of the mesenteric arteries (MAs) was assessed in vitro. Whole-cell patch clamp recordings were used to investigate BK Ca channel function. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect mRNA and protein levels., Results: A significant increase in vascular tone and responsiveness to norepinephrine (NE) was observed after the MaxiK channel blocker (IbTX) was administered. This effect was pronounced in BDL animals and can be mimicked by the FXR agonist GW4064 and inhibited by the FXR antagonist Z-guggulsterone (Z-Gu). GW4064 has a similar effect as cholestasis in promoting MaxiK currents in isolated arterial smooth muscle cells (ASMCs), while Z-Gu blunted this effect. The mRNA and protein expression of FXR and MaxiK-β1, but not MaxiK-α, were significantly increased in the BDL group in comparison to the sham. Furthermore, activation or inhibition of FXR promoted or inhibited the mRNA and protein expression of the MaxiK-β1 subunit, respectively., Conclusion: Activation of FXR enhances the capability of the MaxiK channel to regulate vascular tone and leads to vascular hyporesponsiveness in the MAs of BDL rats, which may be mediated by the nonparallel upregulation of MaxiK-α and MaxiK-β1 subunit expression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

Morphological novelties, or key innovations, are instrumental to the diversification of the organisms. In plants, one such innovation is the evolution of zygomorphic flowers, which is thought to promote outcrossing and increase flower morphological diversity. We isolated three allelic mutants from two Mimulus species displaying altered floral symmetry and identified the causal gene as the ortholog of Arabidopsis BLADE-ON-PETIOLE . We found that MlBOP and MlCYC2A physically interact and this BOP-CYC interaction module is highly conserved across the angiosperms. Furthermore, MlBOP self-ubiquitinates and suppresses MlCYC2A self-activation. MlCYC2A, in turn, impedes MlBOP ubiquitination. Thus, this molecular tug-of-war between MlBOP and MlCYC2A fine-tunes the expression of MlCYC2A , contributing to the formation of bilateral symmetry in flowers, a key trait in angiosperm evolution.

It has been well documented that mutations in coding DNA or cis-regulatory elements underlie natural phenotypic variation in many organisms. However, the development of sophisticated functional tools in recent years in a wide range of traditionally non-model systems have revealed many 'unusual suspects' in the molecular bases of phenotypic evolution, including upstream open reading frames (uORFs), cryptic splice sites, and small RNAs. Furthermore, large-scale genome sequencing, especially long-read sequencing, has identified a cornucopia of structural variation underlying phenotypic divergence and elucidated the composition of supergenes that control complex multi-trait polymorphisms. In this review article we highlight recent studies that demonstrate this great diversity of molecular mechanisms producing adaptive genetic variation and the panoply of evolutionary paths leading to the 'grandeur of life'., Competing Interests: Declaration of interests The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The emergence of novel traits is often preceded by a potentiation phase, when all the genetic components necessary for producing the trait are assembled. However, elucidating these potentiating factors is challenging. We have previously shown that an anthocyanin-activating R2R3-MYB, STRIPY, triggers the emergence of a distinct foliar pigmentation pattern in the monkeyflower Mimulus verbenaceus. Here, using forward and reverse genetics approaches, we identify three potentiating factors that pattern STRIPY expression: MvHY5, a master regulator of light signaling that activates STRIPY and is expressed throughout the leaf, and two leaf developmental regulators, MvALOG1 and MvTCP5, that are expressed in opposing gradients along the leaf proximodistal axis and negatively regulate STRIPY. These results provide strong empirical evidence that phenotypic novelties can be potentiated through incorporation into preexisting genetic regulatory networks and highlight the importance of positional information in patterning the novel foliar stripe., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Gastric cancer metastasis is a major cause of poor prognosis. Our previous research showed that methionine restriction (MR) lowers the invasiveness and motility of gastric carcinoma. In this study, we investigated the particular mechanisms of MR on gastric carcinoma metastasis. In vitro, gastric carcinoma cells (AGS, SNU-5, MKN7, KATO III, SNU-1, and MKN45) were grown in an MR medium for 24 h. In vivo, BALB/c mice were given a methionine-free (Met - ) diet. Transwell assays were used to investigate cell invasion and migration. The amounts of Krüppel like factor 10 (KLF10) and cystathionine β-synthase (CBS) were determined using quantitative real-time PCR and Western blot. To determine the relationship between KLF10 and CBS, chromatin immunoprecipitation and a dual-luciferase reporter experiment were used. Hematoxylin-eosin staining was used to detect lung metastasis. Liquid chromatography-mass spectrometry was used to determine cystathionine content. MR therapy had varying effects on the invasion and migration of gastric carcinoma cells AGS, SNU-5, MKN7, KATO III, SNU-1, and MKN45. KLF10 was highly expressed in AGS cells but poorly expressed in KATO III cells. KLF10 improved MR's ability to prevent gastric carcinoma cell invasion and migration. In addition, KLF10 may interact with CBS, facilitating transcription. Further detection revealed that inhibiting the KLF10/CBS-mediated trans-sulfur pathway lowered Met - 's inhibitory effect on lung metastasis development. KLF10 transcription activated CBS, accelerated the trans-sulfur pathway, and increased gastric carcinoma cells' susceptibility to MR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Here we report our preclinical, proof-of-concept testing to assess the ability of a novel device to correct mitral regurgitation. The Milwaukee Heart device aims to enable any cardiac surgeon to perform high-quality mitral valve repair using a standard annuloplasty ring with a crosshatch of microporous, monofilament suture., Methods: Hemodynamic, echocardiographic, and videographic data were collected at baseline, following induction of mitral regurgitation, and after repair using porcine hearts in an ex vivo biosimulator model. A commercially available cardiac prosthesis assessment platform was then used to assess the hydrodynamic characteristics of the study device., Results: Porcine biosimulator pressure and flow metrics exhibited successful correction of mitral regurgitation following device implantation with similar values to baseline. Hydrodynamic results yielded pressure gradients and an effective orifice area comparable to currently approved prostheses., Conclusions: The study device effectively reduced mitral valve regurgitation and improved hemodynamics in our preclinical model with similar biophysical metrics to currently approved devices. Future in vivo trials are needed to evaluate the efficacy, biocompatibility, and freedom from the most likely adverse events, such as device thrombosis, embolic events, and hemolysis., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Nectar guide trichomes play crucial ecological roles in bee-pollinated flowers, as they serve as footholds and guides for foraging bees to access the floral rewards. However, the genetic basis of natural variation in nectar guide trichomes among species remains poorly understood. In this study, we performed genetic analysis of nectar guide trichome variation between two closely related monkeyflower (Mimulus) species, the bumblebee-pollinated Mimulus lewisii and self-pollinated M. parishii. We demonstrate that a MIXTA-like R2R3-MYB gene, GUIDELESS, is a major contributor to the nectar guide trichome length variation between the two species. The short-haired M. parishii carries a recessive allele due to non-synonymous substitutions in a highly conserved motif among MIXTA-like MYB proteins. Furthermore, our results suggest that besides GUIDELESS, additional loci encoding repressors of trichome elongation also contribute to the transition from bumblebee-pollination to selfing. Taken together, these results suggest that during a pollination syndrome switch, changes in seemingly complex traits such as nectar guide trichomes could have a relatively simple genetic basis, involving just a few genes of large effects., (© 2024. The Author(s).)

Ginger (Zingiber officinale Roscoe) is a high-value food and herb worldwide. The quality of ginger is often related to its production regions. In this study, stable isotopes, multiple elements, and metabolites were investigated together to realize ginger origin traceability. Chemometrics showed that ginger samples could be preliminarily separated, and 4 isotopes (δ 13 C, δ 2 H, δ 18 O, and δ 34 S), 12 mineral elements (Rb, Mn, V, Na, Sm, K, Ga, Cd, Al, Ti, Mg, and Li), 1 bioelement (%C), and 143 metabolites were the most important variables for discrimination. Furthermore, three algorithms were introduced, and the fused dataset based on VIP features led to the highest accuracies for origin classification, with predictive rates of 98% for K-nearest neighbor and 100% for support vector machine and random forest. The results demonstrated that isotopic, elemental, and metabolic fingerprints were useful indicators for the geographical origins of Chinese ginger., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The prevention and treatment of gastric cancer has been the focus and difficulty of medical research. We aimed to explore the mechanism of inhibiting migration and invasion of gastric cancer cells by methionine restriction (MR). The human gastric cancer cell lines AGS and MKN45 cultured with complete medium (CM) or medium without methionine were used for in vitro experiments. MKN45 cells were injected tail vein into BALB/c nude mice and then fed with normal diet or methionine diet for in vivo experiments. MR treatment decreased cell migration and invasion, increased E-cadherin expression, decreased N-cadherin and p-p65 expressions, and inhibited nuclear p65 translocation of AGS and MKN45 cells when compared with CM group. MR treatment increased IκBα protein expression and protein stability, and decreased IκBα protein ubiquitination level and TRIM47 expression. TRIM47 interacted with IκBα protein, and overexpression of TRIM47 reversed the regulatory effects of MR. TRIM47 promoted lung metastasis formation and partially attenuated the effect of MR on metastasis formation in vivo compared to normal diet group mice. MR reduces TRIM47 expression, leads to the degradation of IκBα, and then inhibits the translocation of nuclear p65 and the migration and invasion of gastric cancer cells., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

The evolution of genomic incompatibilities causing postzygotic barriers to hybridization is a key step in species divergence. Incompatibilities take 2 general forms-structural divergence between chromosomes leading to severe hybrid sterility in F1 hybrids and epistatic interactions between genes causing reduced fitness of hybrid gametes or zygotes (Dobzhansky-Muller incompatibilities). Despite substantial recent progress in understanding the molecular mechanisms and evolutionary origins of both types of incompatibility, how each behaves across multiple generations of hybridization remains relatively unexplored. Here, we use genetic mapping in F2 and recombinant inbred line (RIL) hybrid populations between the phenotypically divergent but naturally hybridizing monkeyflowers Mimulus cardinalis and M. parishii to characterize the genetic basis of hybrid incompatibility and examine its changing effects over multiple generations of experimental hybridization. In F2s, we found severe hybrid pollen inviability (<50% reduction vs parental genotypes) and pseudolinkage caused by a reciprocal translocation between Chromosomes 6 and 7 in the parental species. RILs retained excess heterozygosity around the translocation breakpoints, which caused substantial pollen inviability when interstitial crossovers had not created compatible heterokaryotypic configurations. Strong transmission ratio distortion and interchromosomal linkage disequilibrium in both F2s and RILs identified a novel 2-locus genic incompatibility causing sex-independent gametophytic (haploid) lethality. The latter interaction eliminated 3 of the expected 9 F2 genotypic classes via F1 gamete loss without detectable effects on the pollen number or viability of F2 double heterozygotes. Along with the mapping of numerous milder incompatibilities, these key findings illuminate the complex genetics of plant hybrid breakdown and are an important step toward understanding the genomic consequences of natural hybridization in this model system., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Anxiety disorders associated with pain are a common health problem. However, the underlying mechanisms remain poorly understood. We aimed to investigate the role of paraventricular nucleus (PVN)-central nucleus of the amygdala (CeA) oxytocinergic projections in anxiety-like behaviors induced by inflammatory pain., Methods: After inflammatory pain induction by complete Freund's adjuvant (CFA), mice underwent elevated plus maze, light-dark transition test, and marble burying test to examine the anxiety-like behaviors. Chemogenetic, optogenetic, and fiber photometry recordings were used to modulate and record the activity of the oxytocinergic projections of the PVN-CeA., Results: The key results are as follows: inflammatory pain-induced anxiety-like behaviors in mice accompanied by decreased activity of PVN oxytocin neurons. Chemogenetic activation of PVN oxytocin neurons prevented pain-related anxiety-like behaviors, whereas inhibition of PVN oxytocin neurons induced anxiety-like behaviors in naïve mice. PVN oxytocin neurons projected directly to the CeA, and microinjection of oxytocin into the CeA blocked anxiety-like behaviors. Inflammatory pain also decreased the activity of CeA neurons, and optogenetic activation of PVN oxytocin -CeA circuit prevented anxiety-like behavior in response to inflammatory pain., Conclusion: The results of our study suggest that oxytocin has anti-anxiety effects and provide novel insights into the role of PVN oxytocin -CeA projections in the regulation of anxiety-like behaviors induced by inflammatory pain., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: The evidence of breast-conserving therapy (BCT) applied in centrally located breast cancer (CLBC) is absent. This study aims to investigate the long-term survival of breast-conserving therapy (BCT) in centrally located breast cancer (CLBC) compared with mastectomy in CLBC and BCT in non-CLBC., Methods: Two hundred ten thousand four hundred nine women with unilateral T1-2 breast cancer undergoing BCT or mastectomy were identified from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier survival curves were assessed via log-rank test. Propensity score matching (PSM) was used to balance baseline features, and the multivariable Cox model was used to estimate the adjusted hazard ratio [HR] and its 95% confidence interval [CI] for breast cancer-specific survival (BCSS) and overall survival (OS)., Results: With a median follow-up of 91 months, the BCSS and OS rates in patients who received BCT were greater than those patients treated with mastectomy in the entire CLBC set. Multivariable Cox analyses showed that CLBC patients who received BCT had better BCSS (HR = 0.67, 95%CI: 0.55-0.80, p < 0.001) and OS (HR = 0.78, 95%CI: 0.68-0.90, p = 0.001) than patients who received a mastectomy, but there were no significant differences of BCSS (HR = 0.65, 95%CI: 0.47-0.90, p = 0.009) and OS (HR = 0.82, 95%CI: 0.65-1.04, p = 0.110) after PSM. In patients treated with BCT, CLBC patients had a similar BCSS (HR = 0.99, 95%CI: 0.87-1.12, p = 0.850) but a worse OS (HR = 1.09, 95%CI: 1.01-1.18, p = 0.040) compared to that of the non-CLBC patient, but there was no significant difference both BCSS (HR = 1.05, 95%CI: 0.88-1.24, p = 0.614) and OS (HR = 1.08, 95%CI: 0.97-1.20, p = 0.168) after PSM., Conclusion: Our findings revealed that BCT should be an acceptable and preferable alternative to mastectomy for well-selected patients with CLBC., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Beetle daisies evolved floral spots that mimic female bee flies to entice mate-seeking males for pollination. A new study shows that these deceptive spots emerged through stepwise co-option of multiple genetic elements, shedding light on the origin of complex phenotypic novelties., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: To analysis the clinical outcomes of concurrent chemoradiotherapy (CCRT) alone based on 10-year results for loco-regionally advanced nasopharyngeal carcinoma (LANPC), so as to provide evidence for individualized treatment strategy and designing appropriate clinical trial for different risk LANPC patients., Methods: Consecutive patients with stage III-IVa (AJCC/UICC 8th) were enrolled in this study. All patients received radical intensity-modulated radiotherapy (IMRT) and concurrent cisplatin chemotherapy (CDDP). The hazard ratios (HRs) of death risk in patients with T3N0 was used as baseline, relative HRs were calculated by a Cox proportional hazard model to classify different death risk patients. Survival curves for the time-to-event endpoints were analyzed by the Kaplan-Meier method and compared using the log-rank test. All statistical tests were conducted at a two-sided level of significance of 0.05., Results: A total of 456 eligible patients were included. With 12-year median follow-up, 10-year overall survival (OS) was 76%. 10-year loco-regionally failure-free survival (LR-FFS), distant failure-free survival (D-FFS) and failure-free survival (FFS) were 72%, 73% and 70%, respectively. Based on the relative hazard ratios (HRs) of death risk, LANPC patients were classified into 3 subgroups, low-risk group (T1-2N2 and T3N0-1) contained 244 patients with HR < 2; medium-risk group (T3N2 and T4N0-1) contained 140 patients with HR of 2 - 5; high-risk group (T4N2 and T1-4N3) contained 72 patients with HR > 5. The 10-year OS for patients in low-, medium-, and high-risk group were 86%, 71% and 52%, respectively. Significantly differences of OS rates were found between each of the two groups (low-risk group vs. medium-risk group, P < 0.001; low-risk group vs. high-risk group, P < 0.001; and medium-risk group vs. high-risk group, P = 0.002, respectively). Grade 3-4 late toxicities included deafness/otitis (9%), xerostomia (4%), temporal lobe injury (5%), cranial neuropathy (4%), peripheral neuropathy (2%), soft tissue damage (2%) and trismus (1%)., Conclusions: Our classification criteria demonstrated that significant heterogeneity in death risk among TN substages for LANPC patients. IMRT plus CDDP alone maybe suitable for low-risk LANPC (T1-2N2 or T3N0-1), but not for medium- and high-risk patients. These prognostic groupings provide a practicable anatomic foundation to guide individualized treatment and select optimal targeting in the future clinical trials., (© 2023. The Author(s).)

Background: The production of Russian sturgeon is expanding rapidly in China but it is necessary to adopt measures to extend the shelf life of sturgeon meat. Previous studies found that sous vide cooking (SVC) at 60 °C increased the protein and lipid oxidation. The addition of antioxidant substances reduced the acceptance of the product. The effect of combination SVC and ultrasound pretreatment was therefore investigated., Results: Results showed that SVC at 50 °C combined with ultrasound effectively restrained the growth of total viable counts (TVC) in samples. Meanwhile, the main dominant genera changed from Pseudomonas to Carnobacterium and the number of microbial species decreased. The odor profile of Russian sturgeon meat was more stable and the lipoxygenase (LOX) activity decreased more rapidly after treating with SVC and ultrasound. Importantly, more stable protein aggregates were formed in samples treated by SVC 50 °C together with ultrasound pretreatment, so the protein and lipid oxidation were slowed during storage. Higher springiness values were obtained and the color of sturgeon meat was lighter under these conditions., Conclusion: The combination of SVC 50 °C and ultrasound pretreatment effectively inhibited the microbial growth of Russian sturgeon meat at lower oxidation levels. These findings theoretically support the preservation and development of sturgeon meat, and the application of SVC technology. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Taxon-specific small RNA loci are widespread in eukaryotic genomes, yet their role in lineage-specific adaptation, phenotypic diversification, and speciation is poorly understood. Here, we report that a speciation locus in monkeyflowers ( Mimulus ), YELLOW UPPER ( YUP ), contains an inverted repeat region that produces small interfering RNAs (siRNAs) in a phased pattern. Although the inverted repeat is derived from a partial duplication of a protein-coding gene that is not involved in flower pigmentation, one of the siRNAs targets and represses a master regulator of floral carotenoid pigmentation. YUP emerged with two protein-coding genes that control other aspects of flower coloration as a "superlocus" in a subclade of Mimulus and has contributed to subsequent phenotypic diversification and pollinator-mediated speciation in the descendant species.

Objective: To investigate the efficacy and safety of treating refractory chemotherapy-induced thrombocytopenia (RCIT) with San Wei Sheng Huo Decoction (SWSHD) as the main formula., Methods: A retrospective study was conducted and the data of RCIT patients treated with SWSHD as the main formula were collected. Changes in peripheral blood platelet (PLT) levels at different time points of treatment were examined and the significant effective rate (SER) and effective rate (ER) were analyzed. We measured the increase in peripheral blood PLT count before and after treatment, analyzed the differences in PLT count increase for different degrees of RCIT treatment, and evaluated the safety of the treatment., Results: A total of 35 cases of RCIT were included in the study. With SWSHD as the main treatment formula, the 2-week ER and SER were 74.29% and 14.29%, respectively, the 2-month ER and SER were 84.38% and 60.50, respectively, and the 1-year ER and SER were 92.31% and 80.77%, respectively. PLT count increased at all time points after treatment compared with that before treatment ( P <0.01). Subgroup analysis showed that, 2 months after treatment started, peripheral blood PLT counts increased by as much as 51.02×10 9 L －1 in the severe RCIT group, higher than that of the moderate RCIT group at 36.58×10 9 L －1 ( P <0.05), and the difference persisted until 1 year after the treatment. No obvious traditional Chinese medicine-related adverse reaction was observed during the treatment., Conclusion: SWSHD takes effect rapidly and its effect is long-lasting and stable. Furthermore, SWSHD has a more significant effect on severe RCIT., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

The origin of phenotypic novelty is one of the most challenging problems in evolutionary biology. Although genetic regulatory network rewiring or co-option has been widely recognised as a major contributor, in most cases how such genetic rewiring/co-option happens is completely unknown. We have studied a novel foliar pigmentation pattern that evolved recently in the monkeyflower species Mimulus verbenaceus. Through genome-wide association tests using wild-collected samples, experimental crosses of laboratory inbred lines, gene expression analyses, and functional assays, we identified an anthocyanin-activating R2R3-MYB gene, STRIPY, as the causal gene triggering the emergence of the discrete, mediolateral anthocyanin stripe in the M. verbenaceus leaf. Chemical mutagenesis revealed the existence of upstream activators and repressors that form a 'hidden' prepattern along the leaf proximodistal axis, potentiating the unique expression pattern of STRIPY. Population genomics analyses did not reveal signatures of positive selection, indicating that nonadaptive processes may be responsible for the establishment of this novel trait in the wild. This study demonstrates that the origin of phenotypic novelty requires at least two separate phases, potentiation and actualisation. The foliar stripe pattern of M. verbenaceus provides an excellent platform to probe the molecular details of both processes in future studies., (© 2022 The Authors. New Phytologist © 2022 New Phytologist Foundation.)

Objective: This study aimed to explore the clinical value of adjuvant chemotherapy (ACT) following concurrent chemo-radiotherapy (CCRT) and induction chemotherapy (ICT) in loco-regionally advanced nasopharyngeal carcinoma (LANC)., Methods: We included 839 newly diagnosed LANC patients in this study. ICT plus CCRT (ICT + CCRT group) was administered to 443 patients, and 396 patients received ACT after ICT plus CCRT (ICT + CCRT + ACT group). Univariate and multivariate Cox regression analyses were carried out. Furthermore, propensity score matching (PSM) was applied to balance the study and control groups., Results: A total of 373 pairs of LANC patients were obtained after PSM analysis. We found that ACT following ICT + CCRT has no significant effect on improving the survival of LANC patients. By further exploring the ICT + CCRT + ACT treatment protocol, we excluded N0-1-positive patients and re-performed PSM in the ICT + CCRT and ICT + CCRT + ACT groups. Each group consisted of 237 patients. Kaplan-Meier analysis revealed that there were differences between the ICT + CCRT and ICT + CCRT + ACT groups in terms of the 5-year overall survival (OS) (78.9% vs. 85.0%, P = 0.034), disease-free survival (DFS) (73.4% vs. 81.7%, P = 0.029), and distant metastasis-free survival (DMFS) (84.9% vs. 76.0%, P = 0.019). In addition, the ICT + CCRT + ACT group had a higher incidence of grade 3/4 acute leukocytopenia/neutropenia., Conclusion: Compared with ICT + CCRT, ACT following ICT plus CCRT can reduce distant metastasis of N2-3-positive LANC and improve the OS and DFS. The results demonstrated the feasibility and clinical utility of ACT following ICT plus CCRT., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Phenotypic evolution is usually attributed to changes in protein function or gene transcription. In principle, mutations that affect protein abundance through enhancing or attenuating protein translation also could be an important source for phenotypic evolution. However, these types of mutations remain largely unexplored in the studies of phenotypic variation in nature. Through fine-scale genetic mapping and functional interrogation, we identify a single nucleotide substitution in an anthocyanin-activating R2R3-MYB gene causing flower color variation between a pair of closely related monkeyflower ( Mimulus ) species, the hummingbird-pollinated Mimulus cardinalis , and self-pollinated Mimulus parishii . This causal mutation is located in the 5' untranslated region and generates an upstream ATG start codon, leading to attenuated protein translation and reduced flower coloration in the self-pollinated species. Together, our results provide empirical support for the role of mutations affecting protein translation, as opposed to protein function or transcript level, in natural phenotypic variation.

Constitutive activation of plant immunity is detrimental to plant growth and development. Here, we uncover the role of a long non-coding RNA (lncRNA) in fine-tuning the balance of plant immunity and growth. We find that a lncRNA termed salicylic acid biogenesis controller 1 (SABC1) suppresses immunity and promotes growth in healthy plants. SABC1 recruits the polycomb repressive complex 2 to its neighboring gene NAC3, which encodes a NAC transcription factor, to decrease NAC3 transcription via H3K27me3. NAC3 activates the transcription of isochorismate synthase 1 (ICS1), a key enzyme catalyzing salicylic acid (SA) biosynthesis. SABC1 thus represses SA production and plant immunity via decreasing NAC3 and ICS1 transcriptions. Upon pathogen infection, SABC1 is downregulated to derepress plant resistance to bacteria and viruses. Together, our findings reveal lncRNA SABC1 as a molecular switch in balancing plant defense and growth by modulating SA biosynthesis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Floral traits often show correlated variation within and among species. For species with fused petals, strong correlations among corolla tube, stamen, and pistil length are particularly prevalent, and these three traits are considered an intra-floral functional module. Pleiotropy has long been implicated in such modular integration of floral traits, but empirical evidence based on actual gene function is scarce. We tested the role of pleiotropy in the expression of intra-floral modularity in the monkeyflower species Mimulus verbenaceus by transgenic manipulation of a homolog of Arabidopsis PRE1 . Downregulation of MvPRE1 by RNA interference resulted in simultaneous decreases in the lengths of corolla tube, petal lobe, stamen, and pistil, but little change in calyx and leaf lengths or organ width. Overexpression of MvPRE1 caused increased corolla tube and stamen lengths, with little effect on other floral traits. Our results suggest that genes like MvPRE1 can indeed regulate multiple floral traits in a functional module but meanwhile have little effect on other modules, and that pleiotropic effects of these genes may have played an important role in the evolution of floral integration and intra-floral modularity., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Chemotherapy resistance of colorectal cancer stem cells (CRC-SCs) has become a major challenge in clinical treatment of cancer. Methionine restriction (MR) enhances the therapeutic effect of chemotherapeutic agents. The aim of this study was to explore the molecular pathways that MR affects the chemotherapeutic sensitivity of CRC-SCs. CD133 + and CD133 - SW480 or SW620 cells were isolated by magnetic-activated cell sorting (MACS). Mouse xenograft tumor model was established by subcutaneous inoculation of CD133 + SW480. MTT assay was used to detect cell viability. Phase distribution of cell cycle was detected by flow cytometry. Western blotting was used to detect drug-resistant related protein expression. miR-320d and transcription factor c-Myc expressions were detected by qRT-PCR. The interaction between miR-320d and c-Myc was verified by luciferase assay. CD133 + SW480 and SW620 cells were more resistant to 5-fluorouracil (5-FU) than CD133 - cells. In vitro and in vivo experiments showed that 5-FU and MR combined therapy further inhibited CD133 + cell activity and ATP binding cassette subfamily G member 2 (ABCG2) expression, and reduced tumor volume compared with drug administration alone. Interference with miR-320d or overexpression of c-Myc reversed the increased chemotherapeutic sensitivity of CRC-SCs induced by synergistic therapy with 5-FU and MR. miR-320d can target and regulate c-Myc. Interference with c-Myc could reverse the increase in cell viability and ABCG2 expression caused by down-regulation of miR-320d. In conclusion, the combined chemotherapy with MR can enhance the chemotherapeutic sensitivity of CRC-SCs by up-regulation of miR-320d to inhibit c-Myc expression, which lays a molecular basis for MR regulation of chemotherapeutic sensitivity of CRC-SCs., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To investigate whether the addition of fluorouracil to docetaxel and cisplatin induction chemotherapy (IC) can truly improve the prognosis of patients with locoregionally advanced nasopharyngeal carcinoma (NPC)., Methods: A total of 801 patients newly diagnosed with non-metastatic locoregionally advanced NPC were included as the subjects. In this study, propensity score matching (PSM) was used for analysis of overall survival (OS), distant metastasis-free survival (DMFS), progression-free survival (PFS) and locoregional relapse-free survival (LRRFS), and the chi-squared test or Fisher's exact test was used to investigate toxic reactions., Results: Patients received treatment with docetaxel and cisplatin (TP) or docetaxel, cisplatin and fluorouracil (TPF). With a median follow-up time of 60 months (range: 5-124 months), the TPF group had better 5-year OS (84.7% vs 79.0%; P = 0.037), PFS (84.6% vs 76.8%; P = 0.008) and DMFS (89.5% vs 82.3%; P = 0.004) than the TP group. After PSM, 258 patients were matched in each cohort. The Kaplan-Meier analysis showed that the 5-year OS, PFS and DMFS were 85.5%, 84.2% and 89.2%, respectively, in the TPF group, higher than the 80.8%, 75.0% and 81.4%, respectively, in the TP group (P = 0.048, 0.009 and 0.006, respectively). Moreover, the multivariate analysis revealed that different IC regimens were independent prognostic factors for PFS and DMFS (P = 0.014 and 0.010, respectively)., Conclusion: This study found that compared with the TP regimen, TPF induction chemotherapy is associated with improved survival in patients with locoregionally advanced NPC. TPF can produce more mucosal and nausea/vomiting adverse reactions than TP., (© 2021 The Authors. Asia-Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)

Worldwide, nasopharyngeal carcinoma (NPC) is a rare head and neck cancer; however, it is a common malignancy in southern China. Radiotherapy is the most important treatment strategy for NPC. However, although radiotherapy is a strong tool to kill cancer cells, paradoxically it also promotes aggressive phenotypes. Therefore, we mimicked the treatment process in NPC cells in vitro. Upon exposure to radiation, a subpopulation of NPC cells gradually developed resistance to radiation and displayed cancer stem-cell characteristics. Radiation-induced stemness largely depends on the accumulation of the antiapoptotic myeloid cell leukemia 1 (MCL-1) protein. Upregulated MCL-1 levels were caused by increased stability and more importantly, enhanced protein synthesis. We showed that repeated ionizing radiation resulted in persistently enhanced reactive oxygen species (ROS) production at a higher basal level, further promoting protein kinase B (AKT) signaling activation. Intracellular ROS and AKT activation form a positive feedback loop in the process of MCL-1 protein synthesis, which in turn induces stemness and radioresistance. AKT/MCL-1 axis inhibition attenuated radiation-induced resistance, providing a potential target to reverse radiation therapy-induced radioresistance., (© 2022. The Author(s).)

This study explores the role of the long noncoding RNA (LncRNA) CRNDE in cisplatin (CDDP) resistance of gastric cancer (GC) cells. Here, we show that LncRNA CRNDE is upregulated in carcinoma tissues and tumor-associated macrophages (TAMs) of GC patients. In vitro experiments show that CRNDE is enriched in M2-polarized macrophage-derived exosomes (M2-exo) and is transferred from M2 macrophages to GC cells via exosomes. Silencing CRNDE in M2-exo reverses the promotional effect of M2-exo on cell proliferation in CDDP-treated GC cells and homograft tumor growth in CDDP-treated nude mice. Mechanistically, CRNDE facilitates neural precursor cell expressed developmentally downregulated protein 4-1 (NEDD4-1)-mediated phosphatase and tensin homolog (PTEN) ubiquitination. Silencing CRNDE in M2-exo enhances the CDDP sensitivity of GC cells treated with M2-exo, which is reduced by PTEN knockdown. Collectively, these data reveal a vital role for CRNDE in CDDP resistance of GC cells and suggest that the upregulation of CRNDE in GC cells may be attributed to the transfer of TAM-derived exosomes., (© 2021 The Authors.)

Background: The occurrence of recurrence and metastasis after treatment is a major challenge in the treatment of gastric cancer. This study was based on the methionine (Met)-dependent characteristics of gastric cancer cells to explore the effect of Met deficiency on the occurrence and development of gastric cancer., Methods: Human gastric cancer cell lines MKN45 and AGS and nude mice model were used to explore how Met affects gastric cancer by regulating lncRNA PVT1., Results: The levels of lncRNA PVT1 in gastric cancer cells and human gastric cancer xenografts of nude mice were down-regulated under the condition of Met deficiency. The cell viability and cell proliferation were declined after MKN45 and SGC-790 cells were cultured in Met-deficient medium. LncRNA PVT1 could affect BNIP3 promoter DNA methylation level through its interaction with DNMT1. Moreover, the silence of lncRNA PVT1 and the up-regulation of BNIP3 level inhibited the gastric cancer cell proliferation. Met deficiency could up-regulate BNIP3 expression by inhibiting the binding of lncRNA PVT1 to DNMT1, and activate mitophagy, thus inhibiting gastric cancer cell proliferation., Conclusion: Our study suggested that Met deficiency could down-regulate the expression of lncRNA PVT1, further demethylated the promoter of BNIP3, thus inhibiting the proliferation of gastric cancer cells by activating mitophagy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Style length is a major determinant of breeding strategies in flowering plants and can vary dramatically between and within species. However, little is known about the genetic and developmental control of style elongation. We characterized the role of two classes of leaf adaxial-abaxial polarity factors, SUPPRESSOR OF GENE SILENCING3 (SGS3) and the YABBY family transcription factors, in the regulation of style elongation in Mimulus lewisii. We also examined the spatiotemporal patterns of auxin response during style development. Loss of SGS3 function led to reduced style length via limiting cell division, and downregulation of YABBY genes by RNA interference resulted in shorter styles by decreasing both cell division and cell elongation. We discovered an auxin response minimum between the stigma and ovary during the early stages of pistil development that marks style differentiation. Subsequent redistribution of auxin response to this region was correlated with style elongation. Auxin response was substantially altered when both SGS3 and YABBY functions were disrupted. We suggest that auxin signaling plays a central role in style elongation and that the way in which auxin signaling controls the different cell division and elongation patterns underpinning natural style length variation is a major question for future research., (© 2021 The Authors. New Phytologist © 2021 New Phytologist Foundation.)

Background: Gastric cancer (GC) derived exosomes (Exos) aggravate GC development by facilitating M2 macrophage polarization and long non-coding RNA (lncRNA) HCG18 was highly expressed in GC. This study aimed to investigate whether the exosomal lncRNA HCG18 regulated the M2 macrophage polarization in GC and the possible mechanism., Methods: The isolated GC cells (GCCs)-Exos were identified using transmission electron microscopy, Nanoparticle Tracking Analysis and Western blot. The GCCs-Exos function was verified by enzyme-linked immunosorbent assay and flow cytometry. Meanwhile, the exosomal lncRNA HCG18 function was determined using thein vitro assays. Furthermore, the underlying mechanism of the exosomal lncRNA HCG18 that regulated M2 macrophage polarization in GC was investigated using dual-luciferase reporter gene assay and RNA pull-down., Results: After the validation of GCCs-Exos, the GCCs-Exos facilitated the M2 macrophage polarization. The in vitro assays confirmed that the exosomal lncRNA HCG18 positively regulated the M2 macrophage polarization. Mechanistically, lncRNA HCG18 bound to miR-875-3p, miR-875-3p bound to KLF4. Furthermore, GCCs-exosomal lncRNA HCG18 elevated the KLF4 expression by decreasing miR-875-3p in macrophages to facilitate M2 macrophage polarization, thus alleviating GC. The in vivo assays clarified that the GCCs-exosomal lncRNA HCG18 restrained the tumor growth of GC induced by M2 macrophages., Conclusion: GCCs-exosomal lncRNA HCG18 elevated KLF4 expression by decreasing miR-875-3p in macrophages to facilitate the M2 macrophage polarization., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The optimal second-line systemic treatment model for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains controversial. A Bayesian network meta-analysis (NMA) was performed to address this issue with regard to efficacy and toxicity., Methods: By searching MEDLINE ( via PubMed), Embase, the Cochrane Central Register of Controlled Trials and Web of Science, we extracted eligible studies. Efficacy, represented as overall survival (OS) and progression-free survival (PFS), and overall toxicity, represented as ≥ grade 3 severe acute events (sAE), were assessed to compare the following 7 treatment models through an NMA: standard-of-care therapy (SoC), single targeted therapy different from SoC (ST), double targeted therapy (DT), targeted therapy combined with chemotherapy (T+C), single immune checkpoint inhibitor therapy (SI), double immune checkpoint inhibitor therapy (DI) and single chemotherapy different from SoC (SC). Rank probabilities according to the values of the surface under the cumulative ranking curve (SUCRA) were separately determined for efficacy and toxicity., Results: In total, 5285 patients from 24 eligible studies were ultimately screened, with 5184, 4532 and 4026 involved in the NMA of OS, PFS and sAE, respectively. All qualifying studies were absent from first-line immune checkpoint inhibitor therapy. In terms of OS, SI was superior to the other treatments, followed by DI, ST, T+C, SoC, DT and SC. Other than SI and SC, all treatments tended to be consistent, with hazard ratios (HRs) close to 1 between groups. For PFS, ST ranked first, while DT ranked last. For the toxicity profiles, compared with the other models, SI resulted in the lowest incidences of sAE, with statistical significance over SoC (odds ratio [OR] 0.31, 95% credible interval [CrI] 0.11 to 0.90), ST (OR 0.23, 95% CrI 0.06 to 0.86) and DT (OR 0.11, 95% CrI 0.02 to 0.53), while DT was the worst. When the SUCRA values of OS and sAE were combined, a cluster plot illustrated the superiority of SI, which demonstrated the best OS and tolerability toward sAE., Conclusion: For R/M HNSCC patients without immune checkpoint inhibitors in the first-line setting, SI may serve as the optimal second-line systemic treatment model, demonstrating the best OS and least sAE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhan, Yao, Zhang, Qiu, Liao, Feng, Tan, Liu, Yuan, Zheng and Yuan.)

Anthocyanins play a variety of adaptive roles in both vegetative tissues and reproductive organs of plants. The broad functionality of these compounds requires sophisticated regulation of the anthocyanin biosynthesis pathway to allow proper localization, timing, and optimal intensity of pigment deposition. While it is well-established that the committed steps of anthocyanin biosynthesis are activated by a highly conserved MYB-bHLH-WDR (MBW) protein complex in virtually all flowering plants, anthocyanin repression seems to be achieved by a wide variety of protein and small RNA families that function in different tissue types and in response to different developmental, environmental, and hormonal cues. In this review, we survey recent progress in the identification of anthocyanin repressors and the characterization of their molecular mechanisms. We find that these seemingly very different repression modules act through a remarkably similar logic, the so-called 'double-negative logic'. Much of the double-negative regulation of anthocyanin production involves signal-induced degradation or sequestration of the repressors from the MBW protein complex. We discuss the functional and evolutionary advantages of this logic design compared with simple or sequential positive regulation. These advantages provide a plausible explanation as to why plants have evolved so many anthocyanin repressors., (© 2021 The Authors. New Phytologist © 2021 New Phytologist Foundation.)

Fusion of petals to form a corolla tube is considered a key innovation contributing to the diversification of many flowering plant lineages. Corolla tube length often varies dramatically among species and is a major determinant of pollinator preference. However, our understanding of the developmental dynamics underlying corolla tube length variation is very limited. Here we examined corolla tube growth in the Mimulus lewisii species complex, an emerging model system for studying the developmental genetics and evo-devo of pollinator-associated floral traits. We compared developmental and cellular processes associated with corolla tube length variation among the bee-pollinated M. lewisii, the hummingbird-pollinated Mimulus verbenaceus, and the self-pollinated Mimulus parishii. We found that in all three species, cell size is non-uniformly distributed along the mature tube, with the longest cells just distal to the stamen insertion site. Differences in corolla tube length among the three species are not associated with processes of organogenesis or early development but are associated with variation in multiple processes occurring later in development, including the location and duration of cell division and cell elongation. The tube growth curves of the small-flowered M. parishii and large-flowered M. lewisii are essentially indistinguishable, except that M. parishii tubes stop growing earlier at a smaller size, suggesting a critical role of heterochrony in the shift from outcrossing to selfing. These results not only highlight the developmental process associated with corolla tube variation among species but also provide a baseline reference for future developmental genetic analyses of mutants or transgenic plants with altered corolla tube morphology in this emerging model system., (© 2021 Wiley Periodicals LLC.)

Eukaryotic cells contain numerous membraneless organelles that are made from liquid droplets of proteins and nucleic acids and that provide spatiotemporal control of various cellular processes. However, the molecular mechanisms underlying the formation and rapid stress-induced alterations of these organelles are relatively uncharacterized. Here, we investigated the roles of DEAD-box helicases in the formation and alteration of membraneless nuclear dicing bodies (D-bodies) in Arabidopsis thaliana We uncovered that RNA helicase 6 (RH6), RH8, and RH12 are previously unidentified D-body components. These helicases interact with and promote the phase separation of SERRATE, a key component of D-bodies, and drive the formation of D-bodies through liquid-liquid phase separations (LLPSs). The accumulation of these helicases in the nuclei decreases upon Turnip mosaic virus infections, which couples with the decrease of D-bodies. Our results thus reveal the key roles of RH6, RH8, and RH12 in modulating D-body formation via LLPSs., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Background/aims: Targeted drug delivery vehicles with low immunogenicity and toxicity are needed for cancer therapy. Here, we prepare an active targeting drug carrier of low immunogenicity and toxicity for targeted therapy., Methods: Immature dendritic cells (imDCs) from BALB/c mice were used as donor cells of exosomes (Exos) that were transfected with the plasmids expressing fusion proteins of a tumor-targeting peptide known as internalizing RGD (iRGD) to construct a type of tumor-targeting iRGD-Exos and observe the interaction between these iRGD-Exos. Also, recombinant methioninase (rMETase) was loaded into the iRGD-Exos by electroporation to construct iRGD-Exos-rMETase and to assess the tumor-targeting function of the iRGD-Exos-rMETase. Finally, 30 BALB/c were randomly divided into five groups (n = 6), to observe tumor growth in vivo., Results: The iRGD-Exos-rMETase was 99.58 nm in diameter and presented a unique "goblet" structure under transmission electron microscopy (TEM), with the encapsulation efficiency (EE) of 19.05%. iRGD-Exos-rMETase group has the strongest tumor suppressive effect. Compared to the iRGD-Exos-rMETase group, rMETase group and the blank-Exos-rMETase group were less effective, while the PBS group and the iRGD-Exos group showed no inhibitory effect on tumor growth. After treatment, the iRGD-Exos-rMETase group had gastric tumors significantly smaller and lighter than the other groups (P < 0.05)., Conclusion: The iRGD-Exos-rMETase is an effective antitumor therapy that delivers rMETase to tumor tissue using the iRGD-Exos. With its favorable inhibitory effect and tumor-targeting function, the iRGD-Exos-rMETase shows excellent potential value and exciting prospects in clinical applications.

Inferences about past processes of adaptation and speciation require a gene-scale and genome-wide understanding of the evolutionary history of diverging taxa. In this study, we use genome-wide capture of nuclear gene sequences, plus skimming of organellar sequences, to investigate the phylogenomics of monkeyflowers in Mimulus section Erythranthe (27 accessions from seven species). Taxa within Erythranthe, particularly the parapatric and putatively sister species M. lewisii (bee-pollinated) and M. cardinalis (hummingbird-pollinated), have been a model system for investigating the ecological genetics of speciation and adaptation for over five decades. Across >8000 nuclear loci, multiple methods resolve a predominant species tree in which M. cardinalis groups with other hummingbird-pollinated taxa (37% of gene trees), rather than being sister to M. lewisii (32% of gene trees). We independently corroborate a single evolution of hummingbird pollination syndrome in Erythranthe by demonstrating functional redundancy in genetic complementation tests of floral traits in hybrids; together, these analyses overturn a textbook case of pollination-syndrome convergence. Strong asymmetries in allele sharing (Patterson's D-statistic and related tests) indicate that gene tree discordance reflects ancient and recent introgression rather than incomplete lineage sorting. Consistent with abundant introgression blurring the history of divergence, low-recombination and adaptation-associated regions support the new species tree, while high-recombination regions generate phylogenetic evidence for sister status for M. lewisii and M. cardinalis. Population-level sampling of core taxa also revealed two instances of chloroplast capture, with Sierran M. lewisii and Southern Californian M. parishii each carrying organelle genomes nested within respective sympatric M. cardinalis clades. A recent organellar transfer from M. cardinalis, an outcrosser where selfish cytonuclear dynamics are more likely, may account for the unexpected cytoplasmic male sterility effects of selfer M. parishii organelles in hybrids with M. lewisii. Overall, our phylogenomic results reveal extensive reticulation throughout the evolutionary history of a classic monkeyflower radiation, suggesting that natural selection (re-)assembles and maintains species-diagnostic traits and barriers in the face of gene flow. Our findings further underline the challenges, even in reproductively isolated species, in distinguishing re-use of adaptive alleles from true convergence and emphasize the value of a phylogenomic framework for reconstructing the evolutionary genetics of adaptation and speciation., Competing Interests: The authors have declared that no competing interests exist.

Much of the visual diversity of angiosperms is due to the frequent evolution of novel pigmentation patterns in flowers. The gene network responsible for anthocyanin pigmentation, in particular, has become a model for investigating how genetic changes give rise to phenotypic innovation. In the monkeyflower genus Mimulus, an evolutionarily recent gain of petal lobe anthocyanin pigmentation in M. luteus var. variegatus was previously mapped to genomic region pla2. Here, we use sequence and expression analysis, followed by transgenic manipulation of gene expression, to identify MYB5a-orthologous to the NEGAN transcriptional activator from M. lewisii-as the gene responsible for the transition to anthocyanin-pigmented petals in M. l. variegatus. In other monkeyflower taxa, MYB5a/NEGAN is part of a reaction-diffusion network that produces semi-repeating spotting patterns, such as the array of spots in the nectar guides of both M. lewisii and M. guttatus. Its co-option for the evolution of an apparently non-patterned trait-the solid petal lobe pigmentation of M. l. variegatus-illustrates how reaction-diffusion can contribute to evolutionary novelty in non-obvious ways. Transcriptome sequencing of a MYB5a RNAi line of M. l. variegatus reveals that this genetically simple change, which we hypothesize to be a regulatory mutation in cis to MYB5a, has cascading effects on gene expression, not only on the enzyme-encoding genes traditionally thought of as the targets of MYB5a but also on all of its known partners in the anthocyanin regulatory network., (© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.)

Objective : To investigate the clinical value of induction chemotherapy (IC) with docetaxel plus cisplatin (TP) followed by concurrent chemoradiotherapy (CCRT) with TP in locoregionally advanced nasopharyngeal carcinoma (NPC). Methods : A total of 544 patients with locoregionally advanced NPC that was newly diagnosed from January 2009 to December 2015 were included in this study. Among these patients, 251 were treated with TP induction chemotherapy followed by CCRT with cisplatin (DDP) alone (TP + DDP group), 167 were treated with TP followed by CCRT with TP (TP + TP group), and 126 were treated with docetaxel, DDP and fluorouracil (TPF) followed by CCRT with DDP alone (TPF + DDP group). Overall survival (OS), distant metastasis-free survival (DMFS), progression-free survival (PFS) and locoregional relapse-free survival (LRRFS) were analyzed using the Kaplan-Meier method and a Cox proportional hazards model. Results : Survival analysis showed that the 5-year OS, PFS and DMFS rates in the TP + DDP group were significantly lower than those in the TP + TP group after propensity score matching (PSM). Multivariate analysis revealed that CCRT with TP was an independent prognostic factor for OS, PFS and DMFS. During CCRT, the incidence rates of grade 3/4 nausea/vomiting, oral mucositis, leukocytopenia and neutropenia were significantly increased in the TP + TP group compared with the TP + DDP group (all P < 0.05). To further explore the value of TP + TP, we performed PSM again with the TPF + DDP group. After PSM, there were 100 patients in each group. Survival analysis showed no significant differences in the 5-year OS, PFS, DMFS and LRRFS rates between the two groups. During IC and CCRT, the rate of grade 3/4 nausea/vomiting in the TPF + DDP group was higher than that in the TP+TP group (9.0% vs. 2.0%, P = 0.030; 18.0% vs. 8.0%, P = 0.036, respectively). No significant difference in the incidence of grade 3/4 hematologic toxicity was found between the two groups (all P > 0.05). Conclusion : TP + TP can reduce the distant metastasis of locoregionally advanced NPC and improve OS compared with TP + DDP; TP + TP has the same effect as TPF + DDP and is clinically feasible., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Over 80,000 angiosperm species produce flowers with petals fused into a corolla tube. The corolla tube contributes to the tremendous diversity of flower morphology and plays a critical role in plant reproduction, yet it remains one of the least understood plant structures from a developmental genetics perspective. Through mutant analyses and transgenic experiments, we show that the tasiRNA- ARF pathway is required for corolla tube formation in the monkeyflower species Mimulus lewisii Loss-of-function mutations in the M. lewisii orthologs of ARGONAUTE7 and SUPPRESSOR OF GENE SILENCING3 cause a dramatic decrease in abundance of TAS3 -derived small RNAs and a moderate upregulation of AUXIN RESPONSE FACTOR3 ( ARF3 ) and ARF4 , which lead to inhibition of lateral expansion of the bases of petal primordia and complete arrest of the upward growth of the interprimordial regions, resulting in unfused corollas. Using the DR5 auxin-responsive promoter, we discovered that auxin signaling is continuous along the petal primordium base and the interprimordial region during the critical stage of corolla tube formation in the wild type, similar to the spatial pattern of MlARF4 expression. Auxin response is much weaker and more restricted in the mutant. Furthermore, exogenous application of a polar auxin transport inhibitor to wild-type floral apices disrupted petal fusion. Together, these results suggest a new conceptual model highlighting the central role of auxin-directed synchronized growth of the petal primordium base and the interprimordial region in corolla tube formation., (© 2020 American Society of Plant Biologists. All rights reserved.)