Associations between immune cell phenotypes and lung cancer subtypes: insights from mendelian randomization analysis.

INTRODUCTION: Lung cancer is a common malignant tumor, and different types of immune cells may have different effects on the occurrence and development of lung cancer subtypes, including lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). However, the causal relationship between immune phenotype and lung cancer is still unclear. METHODS: This study utilized a comprehensive dataset containing 731 immune phenotypes from the European Bioinformatics Institute (EBI) to evaluate the potential causal relationship between immune phenotypes and LUSC and LUAD using the inverse variance weighted (IVW) method in Mendelian randomization (MR). Sensitivity analyses, including MR-Egger intercept, Cochran Q test, and others, were conducted for the robustness of the results. The study results were further validated through meta-analysis using data from the Transdisciplinary Research Into Cancer of the Lung (TRICL) data. Additionally, confounding factors were excluded to ensure the robustness of the findings. RESULTS: Among the final selection of 729 immune cell phenotypes, three immune phenotypes exhibited statistically significant effects with LUSC. CD28 expression on resting CD4 regulatory T cells (OR 1.0980, 95% CI: 1.0627-1.1344, p < 0.0001) and CD45RA + CD28- CD8 + T cell %T cell (OR 1.0011, 95% CI: 1.0007; 1.0015, p < 0.0001) were associated with increased susceptibility to LUSC. Conversely, CCR2 expression on monocytes (OR 0.9399, 95% CI: 0.9177-0.9625, p < 0.0001) was correlated with a decreased risk of LUSC. However, no significant causal relationships were established between any immune cell phenotypes and LUAD. CONCLUSION: This study demonstrates that specific immune cell types are associated with the risk of LUSC but not with LUAD. While these findings are derived solely from European populations, they still provide clues for a deeper understanding of the immunological mechanisms underlying lung cancer and may offer new directions for future therapeutic strategies and preventive measures.

Insights into cell wall changes during fruit softening from transgenic and naturally occurring mutants.

Excessive softening during fleshy fruit ripening leads to physical damage and infection that reduce quality and cause massive supply chain losses. Changes in cell wall (CW) metabolism, involving loosening and disassembly of the constituent macromolecules, are the main cause of softening. Several genes encoding CW metabolizing enzymes have been targeted for genetic modification to attenuate softening. At least 9 genes encoding CW-modifying proteins have increased expression during ripening. Any alteration of these genes could modify CW structure and properties and contribute to softening, but evidence for their relative importance is sparse. The results of studies with transgenic tomato (Solanum lycopersicum), the model for fleshy fruit ripening, investigations with strawberry (Fragaria spp.) and apple (Malus domestica), and results from naturally occurring textural mutants provide direct evidence of gene function and the contribution of CW biochemical modifications to fruit softening. Here we review the revised CW structure model and biochemical and structural changes in CW components during fruit softening and then focus on and integrate the results of changes in CW characteristics derived from studies on transgenic fruits and mutants. Potential strategies and future research directions to understand and control the rate of fruit softening are also discussed.

Abscisic acid mediated strawberry receptacle ripening involves the interplay of multiple phytohormone signaling networks.

As a canonical non-climacteric fruit, strawberry (Fragaria spp.) ripening is mainly mediated by abscisic acid (ABA), which involves multiple other phytohormone signalings. Many details of these complex associations are not well understood. We present an coexpression network, involving ABA and other phytohormone signalings, based on weighted gene coexpression network analysis of spatiotemporally resolved transcriptome data and phenotypic changes of strawberry receptacles during development and following various treatments. This coexpression network consists of 18,998 transcripts and includes transcripts related to phytohormone signaling pathways, MADS and NAC family transcription factors and biosynthetic pathways associated with fruit quality. Members of eight phytohormone signaling pathways are predicted to participate in ripening and fruit quality attributes mediated by ABA, of which 43 transcripts were screened to consist of the hub phytohormone signalings. In addition to using several genes reported from previous studies to verify the reliability and accuracy of this network, we explored the role of two hub signalings, small auxin up-regulated RNA 1 and 2 in receptacle ripening mediated by ABA, which are also predicted to contribute to fruit quality. These results and publicly accessible datasets provide a valuable resource to elucidate ripening and quality formation mediated by ABA and involves multiple other phytohormone signalings in strawberry receptacle and serve as a model for other non-climacteric fruits.

Roles of abscisic acid in regulating ripening and quality of strawberry, a model non-climacteric fruit.

Abscisic acid (ABA) is a dominant regulator of ripening and quality in non-climacteric fruits. Strawberry is regarded as a model non-climacteric fruit due to its extensive genetic studies and proven suitability for transgenic approaches to understanding gene function. Strawberry research has contributed to studies on color, flavor development, and fruit softening, and in recent years ABA has been established as a core regulator of strawberry fruit ripening, whereas ethylene plays this role in climacteric fruits. Despite this major difference, several components of the interacting genetic regulatory network in strawberry, such as MADS-box and NAC transcription factors, are similar to those that operate in climacteric fruit. In this review, we summarize recent advances in understanding the role of ABA biosynthesis and signaling and the regulatory network of transcription factors and other phytohormones in strawberry fruit ripening. In addition to providing an update on its ripening, we discuss how strawberry research has helped generate a broader and more comprehensive understanding of the mechanism of non-climacteric fruit ripening and focus attention on the use of strawberry as a model platform for ripening studies.

Transcriptional regulation of fleshy fruit texture.

Fleshy fruit texture is a critically important quality characteristic of ripe fruit. Softening is an irreversible process which operates in most fleshy fruits during ripening which, together with changes in color and taste, contributes to improvements in mouthfeel and general attractiveness. Softening results mainly from the expression of genes encoding enzymes responsible for cell wall modifications but starch degradation and high levels of flavonoids can also contribute to texture change. Some fleshy fruit undergo lignification during development and post-harvest, which negatively affects eating quality. Excessive softening can also lead to physical damage and infection, particularly during transport and storage which causes severe supply chain losses. Many transcription factors (TFs) that regulate fruit texture by controlling the expression of genes involved in cell wall and starch metabolism have been characterized. Some TFs directly regulate cell wall targets, while others act as part of a broader regulatory program governing several aspects of the ripening process. In this review, we focus on advances in our understanding of the transcriptional regulatory mechanisms governing fruit textural change during fruit development, ripening and post-harvest. Potential targets for breeding and future research directions for the control of texture and quality improvement are discussed.

R2R3-MYB genes coordinate conical cell development and cuticular wax biosynthesis in Phalaenopsis aphrodite.

Petals of the monocot Phalaenopsis aphrodite (Orchidaceae) possess conical epidermal cells on their adaxial surfaces, and a large amount of cuticular wax is deposited on them to serve as a primary barrier against biotic and abiotic stresses. It has been widely reported that subgroup 9A members of the R2R3-MYB gene family, MIXTA and MIXTA-like in eudicots, act to regulate the differentiation of conical epidermal cells. However, the molecular pathways underlying conical epidermal cell development and cuticular wax biosynthesis in monocot petals remain unclear. Here, we characterized two subgroup 9A R2R3-MYB genes, PaMYB9A1 and PaMYB9A2 (PaMYB9A1/2), from P. aphrodite through the transient overexpression of their coding sequences and corresponding chimeric repressors in developing petals. We showed that PaMYB9A1/2 function to coordinate conical epidermal cell development and cuticular wax biosynthesis. In addition, we identified putative targets of PaMYB9A1/2 through comparative transcriptome analyses, revealing that PaMYB9A1/2 acts to regulate the expression of cell wall-associated and wax biosynthetic genes. Furthermore, a chemical composition analysis of cuticular wax showed that even-chain n-alkanes and odd-chain primary alcohols are the main chemical constituents of cuticular wax deposited on petals, which is inconsistent with the well-known biosynthetic pathways of cuticular wax, implying a distinct biosynthetic pathway occurring in P. aphrodite flowers. These results reveal that the function of subgroup 9A R2R3-MYB family genes in regulating the differentiation of epidermal cells is largely conserved in monocots and dicots. Furthermore, both PaMYB9A1/2 have evolved additional functions controlling the biosynthesis of cuticular wax.

The Cymbidium genome reveals the evolution of unique morphological traits.

The marvelously diverse Orchidaceae constitutes the largest family of angiosperms. The genus Cymbidium in Orchidaceae is well known for its unique vegetation, floral morphology, and flower scent traits. Here, a chromosome-scale assembly of the genome of Cymbidium ensifolium (Jianlan) is presented. Comparative genomic analysis showed that C. ensifolium has experienced two whole-genome duplication (WGD) events, the most recent of which was shared by all orchids, while the older event was the τ event shared by most monocots. The results of MADS-box genes analysis provided support for establishing a unique gene model of orchid flower development regulation, and flower shape mutations in C. ensifolium were shown to be associated with the abnormal expression of MADS-box genes. The most abundant floral scent components identified included methyl jasmonate, acacia alcohol and linalool, and the genes involved in the floral scent component network of C. ensifolium were determined. Furthermore, the decreased expression of photosynthesis-antennae and photosynthesis metabolic pathway genes in leaves was shown to result in colorful striped leaves, while the increased expression of MADS-box genes in leaves led to perianth-like leaves. Our results provide fundamental insights into orchid evolution and diversification.

Epidemiological and clinical characteristics of fifty-six cases of COVID-19 in Liaoning Province, China.

BACKGROUND: Pneumonia of uncertain cause has been reported in Wuhan, China since the beginning of early December 2019. In early January 2020, a novel strain of ß-coronavirus was identified by the Chinese Center for Disease Control and Prevention from the pharyngeal swab specimens of patients, which was recently named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is evidence of human-to-human transmission and familial cluster outbreak of SARS-CoV-2 infection. The World Health Organization(WHO) recently declared the SARS-CoV-2 epidemic a global health emergency. As of February 17, 2020, 71329 laboratory-confirmed cases (in 25 countries, including the United States and Germany) have been reported globally. Other than its rapid transmission, the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) remain unclear. In December 2019, coronavirus disease (named COVID-19 by the WHO) associated with the SARS-CoV-2 emerged in Wuhan, China and spread quickly across the country. AIM: To analyze the epidemiological and clinical characteristics of confirmed cases of this disease in Liaoning province, a Chinese region about 1800 km north of Wuhan. METHODS: The clinical data of 56 laboratory-confirmed COVID-19 cases due to 2019-nCoV infection were analyzed. The cases originated from eight cities in Liaoning province. RESULTS: The median age of the patients was 45 years, and 57.1% of them were male. No patient had been in direct contact with wild animals. Among them, 23 patients (41.1%) had resided in or traveled to Wuhan, 27 cases (48.2%) had been in contact with confirmed COVID-19 patients, 5 cases (8.9%) had been in contact with confirmed patients with a contact history to COVID-19 patients, and 1 case (1.8%) had no apparent history of exposure. Fever (75.0%) and cough (60.7%) were the most common symptoms. The typical manifestations in lung computed tomography (CT) included ground-glass opacity and patchy shadows, with 67.8% of them being bilateral. Among the patients in the cohort, 78.6% showed reduction in their lymphocyte counts, 57.1% showed increases in their C-reactive protein levels, and 50.0% showed decreases in their blood albumin levels. Eleven patients (19.6%) were admitted to intensive care unit, 2 patients (3.5%) progressed to acute respiratory distress syndrome, 4 patients (7.1%) were equipped with non-invasive mechanical ventilation, and 1 patient (1.8) received extracorporeal membrane oxygenation support. There were 5 mild cases (5/56, 8.9%), 40 moderate cases (40/56, 71.4%), 10 severe cases (10/56, 17.9%), and 1 critical case (1/56, 1.8%). No deaths were reported. CONCLUSION: SARS-CoV-2 can be transmitted among humans. Most COVID-19 patients show symptoms of fever, cough, lymphocyte reduction, and typical lung CT manifestations. Most are moderate cases. The seriousness of the disease (as indicated by blood oxygen saturation, respiratory rate, oxygenation index, blood lymphocyte count, and lesions shown in lung CT) is related to history of living in or traveling to Wuhan, underlying diseases, admittance to intensive care unit, and mechanical ventilation.

New insight into the molecular mechanism of colour differentiation among floral segments in orchids.

An unbalanced pigment distribution among the sepal and petal segments results in various colour patterns of orchid flowers. Here, we explored this type of mechanism of colour pattern formation in flowers of the Cattleya hybrid 'KOVA'. Our study showed that pigment accumulation displayed obvious spatiotemporal specificity in the flowers and was likely regulated by three R2R3-MYB transcription factors. Before flowering, RcPAP1 was specifically expressed in the epichile to activate the anthocyanin biosynthesis pathway, which caused substantial cyanin accumulation and resulted in a purple-red colour. After flowering, the expression of RcPAP2 resulted in a low level of cyanin accumulation in the perianths and a pale pink colour, whereas RcPCP1 was expressed only in the hypochile, where it promoted α-carotene and lutein accumulation and resulted in a yellow colour. Additionally, we propose that the spatiotemporal expression of different combinations of AP3- and AGL6-like genes might participate in KOVA flower colour pattern formation.

RNA-seq transcriptomic profiling of crassulacean acid metabolism pathway in Dendrobium catenatum.

The regulation of crassulacean acid metabolism (CAM) pathway has recently become a topic of intensive research and has been explored in terms of several aspects, including phylogenetics, genomics, and transcriptomics. Orchidaceae, which contains approximately 9,000 CAM species, is one of the largest lineages using this special photosynthetic pathway. However, no comprehensive transcriptomic profiling focused on CAM regulation in orchid species had previously been performed. In this report, we present two Illumina RNA-seq datasets, including a total of 24 mature leaf samples with 844.4 million reads, from Dendrobium catenatum (Orchidaceae), a facultative CAM species. The first dataset was generated from a time-course experiment based on the typical CAM phases in a diel. The second was derived from an experiment on drought stress and stress removal. A series of quality assessments were conducted to verify the reliability of the datasets. These transcriptomic profiling datasets will be useful to explore and understand the essence of CAM regulation.

Genetic diversity and ex situ conservation of Loropetalum subcordatum, an endangered species endemic to China.

BACKGROUND: Loropetalum subcordatum is an endangered species endemic to China that is characterized by narrow distribution, small population size, and delayed fertilization. However, the genetic diversity of the entire extant natural and ex situ populations has not been assessed to date. In this study, we evaluated the genetic diversity and structure of six natural populations and a single ex situ population (the only known ex situ population of L. subcordatum) using sequence-related amplified polymorphism data. RESULTS: In total, 553 reliable DNA bands, of which 359 (63.28%) were polymorphic, were amplified by polymerase chain reaction with combinations of 15 primers. Low average gene diversity within populations and high genetic differentiation were detected in L. subcordatum. A Mantel test demonstrated that there was a positive correlation between genetic and geographic distances, indicating that significant genetic divergence was likely the result of geographic isolation among natural populations. Furthermore, based on genetic structure patterns, populations of L. subcordatum were divided into three clusters. Group 1 was composed of specimens from Libo, Guizhou Province (GZ) and Huanjiang, Guangxi Zhuang Autonomous Region (GX). Group 2 was composed of Mt. Wuguishan, Guangdong Province (GD). Group 3 was composed of three populations in Hong Kong Special Administrative Region. Additionally, clonal reproduction probably existed in GD population. According to the genetic information analysis and field survey, the ex situ population did not match its source population (GD) in terms of genetics, and its habitat was different from the original natural habitat. We observed that a few individual GD seeds were needed to improve ZS ex situ in the future. CONCLUSIONS: Compared to previous SRAP-based studies of endangered plants, L. subcordatum had extremely low average gene diversity within populations and high genetic differentiation among populations. At present, the unique ex situ population has not been successful due to non-representative samples being taken, a smaller population size, and man-made changes in habitat. Potential strategies are suggested to improve the conservation of this species.

Transforming growth factor-ß1 induces matrix metalloproteinase-9 expression in rat vascular smooth muscle cells via ROS-dependent ERK-NF-κB pathways.

Both matrix metalloproteinase-9 (MMP9) and transforming growth factors-ß1 (TGF-ß1) are the important factors in the pathogenesis of the aortic aneurysm (AA) and aortic dissection (AD). Recent studies have shown that inhibition of reactive oxygen species (ROS) production, extracellular signal-regulated kinase 1/2(ERK1/2) or NF-κB pathways is able to suppress aneurysm formation. The median layers of arterial walls are mainly the vascular smooth muscle cells (VSMCs), while the pathogenesis of AA and AD is closely related to the changes in the median layer structure. Thus, we investigated the molecular mechanisms underlying TGF-ß1-induced MMP-9 expression in VSMC, the involvement of intracellular ROS and signaling molecules, including ERK1/2 and NF-κB. Rat vascular smooth muscle cells (A7r5) were used. MMP-9 expression was analyzed by gelatin zymography, western blot and RT-PCR. The involvement of intracellular ROS and signaling molecules including ERK1/2 and NF-κB in the responses was investigated using reactive oxygen scavenger N-acetylcysteine (NAC) and pharmacological inhibitors (U0126 and BAY11-7082), determined by ROS testing and western blot testing for their corresponding proteins. TGF-ß1 induces MMP-9 expression via ROS-dependent signaling pathway. ROS production leads to activation of ERK1/2 and then activation of the NF-κB transcription factor. Activated NF-κB turns on transcription of the MMP-9 gene. The process in which TGF-ß1 induces MMP9 expression involves the ROS-dependent ERK-NF-κB signal pathways in VSMC. This discovery raises a new regulation pathway in the VSMC, and it shows the potential to help to find a new solution to treating aortic aneurysm and aortic dissection.