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1.
Proc Natl Acad Sci U S A ; 119(18): e2105006119, 2022 05 03.
Article in English | MEDLINE | ID: mdl-35467985

ABSTRACT

The world has committed trillions in fiscal expenditures to reboot the economy in the post­COVID-19 era. However, the effectiveness and the equity impacts of current fiscal stimuli are not fully understood. Using an extended adaptive regional input­output model, we assess the short-term impacts (2020 through 2022) of feasible stimuli on the global economy and the labor market. Our findings show that the stimuli pledged by 26 countries, i.e., 2.4 trillion euros in total, are effective in keeping the recession short and shallow by saving 53 million to 57 million jobs (compared to the no-stimulus scenario). However, the stimuli exacerbate income inequity at the global scale if we define "equity" as those who suffer more from the pandemic should receive more assistance. Low-skilled workers in these countries, who suffer more from the pandemic than high-skilled workers, benefit 38 to 41% less from the job-creation effects of the current fiscal stimuli. As an alternative, low-carbon stimuli can achieve a balance between effectiveness and equity at the global level. Low-carbon stimuli save 55 million to 58 million jobs and decrease income inequality by 2 to 3% globally compared to the currently pledged stimuli. Country-level situations are more complicated, as modifying the current stimuli to achieve more "greenness" brings win­win in effectiveness and equity in some countries, while in the others, more greenness and equity are at the expense of less job savings. Our findings underscore the need to consider the overlooked trade-offs between effectiveness, equity, and greenness, both globally and nationally, when designing further postpandemic fiscal stimuli.


Subject(s)
Employment , Income , Climate Change , Humans
2.
Plant Physiol ; 191(2): 1017-1035, 2023 02 12.
Article in English | MEDLINE | ID: mdl-36417282

ABSTRACT

The fast growth of Moso bamboo (Phyllostachys edulis) shoots is caused by the rapid elongation of each internode. However, the key underlying cellular processes and epigenetic mechanisms remain largely unexplored. We used microscopy and multi-omics approaches to investigate two regions (bottom and middle) of the 18th internode from shoots of two different heights (2 and 4 m). We observed that internode cells become longer, and that lignin biosynthesis and glycosyltransferase family 43 (GT43) genes are substantially upregulated with shoot height. Nanopore direct RNA sequencing (DRS) revealed a higher N6-methyladenine (m6A) modification rate in 2-m shoots than in 4-m shoots. In addition, different specific m6A modification sites were enriched at different growth stages. Global DNA methylation profiling indicated that DNA methylation levels are higher in 4-m shoots than in 2-m shoots. We also detected shorter poly(A) tail lengths (PALs) in 4-m shoots compared with 2-m shoots. Genes showing differential PAL were mainly enriched in the functional terms of protein translation and vesicle fusion. An association analysis between PALs and DNA methylation strongly suggested that gene body CG methylation levels are positively associated with PAL. This study provides valuable information to better understand post-transcriptional regulations responsible for fast-growing shoots in Moso bamboo.


Subject(s)
Gene Expression Regulation, Plant , Poaceae , Plant Shoots/metabolism , Poaceae/genetics , RNA/metabolism , Epigenesis, Genetic
3.
Chem Res Toxicol ; 37(6): 1062-1069, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38815162

ABSTRACT

Multiple myeloma is a hematological cancer that can be treated but remains incurable. With the advancement of science and technology, more drugs have been developed for myeloma chemotherapy that greatly improve the quality of life of patients. However, relapse remains a serious problem puzzling patients and doctors. Thus, developing more highly active and specific inhibitors is urgent for myeloma-targeted therapy. In this study, we identified the SIRT3 inhibitor 3-TYP (3-(1H-1,2,3-triazol-4-yl) pyridine) after screening a histone modification compound library, which showed high cytotoxicity and induced DNA damage in myeloma cells. Furthermore, the inhibitory effect of 3-TYP in our xenograft tumor studies also confirmed that compound 3-TYP could inhibit primary myeloma growth by reducing c-Myc protein stability by decreasing c-Myc Ser62 phosphorylation levels. Taken together, the results of our study identified 3-TYP as a novel c-Myc inhibitor, which could be a potential chemotherapeutic agent to target multiple myeloma.


Subject(s)
Antineoplastic Agents , Cell Proliferation , Multiple Myeloma , Proto-Oncogene Proteins c-myc , Sirtuin 3 , Multiple Myeloma/drug therapy , Multiple Myeloma/pathology , Multiple Myeloma/metabolism , Humans , Proto-Oncogene Proteins c-myc/antagonists & inhibitors , Proto-Oncogene Proteins c-myc/metabolism , Sirtuin 3/antagonists & inhibitors , Sirtuin 3/metabolism , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Mice , Pyridines/pharmacology , Pyridines/chemistry , Triazoles/pharmacology , Triazoles/chemistry , Cell Line, Tumor , Molecular Structure , Drug Screening Assays, Antitumor , Protein Stability/drug effects , Mice, Nude
4.
Virol J ; 21(1): 107, 2024 05 08.
Article in English | MEDLINE | ID: mdl-38720392

ABSTRACT

Natural immunity is the first defense line of the host immune system, which plays a significant role in combating foreign pathogenic microorganisms. The IFN-ß (interferon-beta) signaling pathway, being a typical example of innate immunity, plays a vital function. This study aimed to elucidate the function of pseudorabies virus (PRV) UL38 protein (unique long region 38) in suppressing the activation of the IFN-ß signaling pathway. The findings from our study indicate that the PRV UL38 protein effectively hampers the activation of IFN-ß by poly (dA: dT) (poly(deoxyadenylic-deoxythymidylic)) and 2'3'-cGAMP (2'-3'-cyclic GMP-AMP). Furthermore, UL38 exhibits spatial co-localization with STING (stimulator of interferon genes) and effectively hinders STING dimerization. Subsequently, STING was downgraded to suppress the production of IFN-ß and ISGs (interferon stimulated genes). Immunoprecipitation analysis revealed that the interaction between UL38 and STING, which subsequently initiated the degradation of STING via selective autophagy mediated by TOLLIP (toll interacting protein). To summarize, this research elucidates the function of UL38 in counteracting the cGAS (cGAMP synthase)-STING-induced IFN-ß pathway. The PRV UL38 protein may attenuate the activation of IFN-ß as a means of regulating the virus's persistence in the host.


Subject(s)
Autophagy , Herpesvirus 1, Suid , Interferon-beta , Membrane Proteins , Nucleotidyltransferases , Signal Transduction , Animals , Humans , Cell Line , HEK293 Cells , Herpesvirus 1, Suid/physiology , Herpesvirus 1, Suid/immunology , Host-Pathogen Interactions , Immunity, Innate , Interferon-beta/metabolism , Interferon-beta/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Membrane Proteins/metabolism , Nucleotidyltransferases/metabolism , Nucleotidyltransferases/genetics , Pseudorabies/virology , Pseudorabies/metabolism , Pseudorabies/immunology , Viral Proteins/metabolism , Viral Proteins/genetics , Swine , Mesocricetus
5.
J Org Chem ; 89(2): 1209-1219, 2024 01 19.
Article in English | MEDLINE | ID: mdl-38192075

ABSTRACT

Guided by the Global Natural Products Social (GNPS) molecular networking strategy, five undescribed eremophilane-type sesquiterpenoid derivatives (1-5) were isolated and identified from fungus Penicillium roqueforti, which was separated from the root soil of plant Hypericum beanii collected in Shennongjia Forestry District, Hubei Province. Dipeniroqueforins A-B (1-2), representing a lactam-type sesquiterpenoid skeleton with a highly symmetrical and homodimeric 5/6/6-6/6/5 hexacyclic system, are reported within the eremophilane-type family for the first time. Peniroqueforin D (5) represents the first example of a 1,2-seco eremophilane-type sesquiterpenoid derivative featuring an undescribed 7/6-fused ring system. The structures of these compounds were elucidated by various spectroscopic analyses, DP4+ probability analyses, ECD calculations, and single-crystal X-ray diffraction experiments. Furthermore, these isolates were evaluated for cytotoxicity, and the result uncovered that compound 1 displayed broad-spectrum activity. Further mechanistic study revealed that compound 1 could significantly upregulate the mRNA expression of genes related to the oxidative induction, leading to the abnormal ROS levels in tumor cells and ultimately causing tumor cell apoptosis.


Subject(s)
Antineoplastic Agents , Penicillium , Sesquiterpenes , Polycyclic Sesquiterpenes , Molecular Structure , Sesquiterpenes/chemistry , Penicillium/chemistry , Antineoplastic Agents/chemistry
6.
Neuroimmunomodulation ; 31(1): 126-141, 2024.
Article in English | MEDLINE | ID: mdl-38843787

ABSTRACT

INTRODUCTION: Dimethyl fumarate (DMF) has shown potential for protection in various animal models of neurological diseases. However, the impact of DMF on changes in peripheral immune organs and the central nervous system (CNS) immune cell composition after ischemic stroke remains unclear. METHODS: Eight-week-old C57BL/6J mice with photothrombosis ischemia and patients with acute ischemic stroke (AIS) were treated with DMF. TTC staining, flow cytometry, and immunofluorescence staining were used to evaluate the infarct volume and changes in immune cells in the periphery and the CNS. RESULTS: DMF reduced the infarct volume on day 1 after PT. DMF reduced the percentages of peripheral immune cells, such as neutrophils, dendritic cells, macrophages, and monocytes, on day 1, followed by NK cells on day 3 and B cells on day 7 after PT. In the CNS, DMF significantly reduced the percentage of monocytes in the brain on day 3 after PT. In addition, DMF increased the number of microglia in the peri-infarct area and reduced the number of neurons in the peri-infarct area in the acute and subacute phases after PT. In AIS patients, B cells decreased in patients receiving alteplase in combination with DMF. CONCLUSION: DMF can change the immune environment of the periphery and the CNS, reduce infarct volume in the acute phase, promote the recruitment of microglia and preserve neurons in the peri-infarct area after ischemic stroke.


Subject(s)
Dimethyl Fumarate , Ischemic Stroke , Mice, Inbred C57BL , Animals , Dimethyl Fumarate/pharmacology , Dimethyl Fumarate/therapeutic use , Ischemic Stroke/immunology , Ischemic Stroke/drug therapy , Mice , Male , Humans , Female , Prognosis , Middle Aged , Aged , Disease Models, Animal
7.
Clin Exp Rheumatol ; 42(4): 843-851, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38607693

ABSTRACT

OBJECTIVES: Coronary artery calcification (CAC) is frequently observed in Takayasu's arteritis (TAK). Our objective is to calculate the prevalence and severity of CAC in TAK, while evaluating the influence of traditional cardiovascular risk factors, glucocorticoid exposure, and disease activity on CAC. METHODS: This retrospective study involved 155 TAK patients. We measured the Agatston score by coronary computed tomography angiography (CCTA) and categorised all patients into groups with or without CAC (41 vs. 114) to compare clinical characteristics and ancillary findings between the two groups. RESULTS: Among the TAK patients, a total of 41 TAK patients (26.45%) exhibited CAC. Age of onset, disease duration, history of hypertension, history of hyperlipidaemia, Numano V and glucocorticoid use emerged as the independent risk factors for developing CAC in TAK (OR [95% CI] 1.084[1.028-1.142], p=0.003; 1.005 [1.001-1.010], p=0.020; 4.792 [1.713-13.411], p=0.003; 4.199 [1.087-16.219], p=0.037; 3.287 [1.070-10.100], p=0.038; 3.558[1.269-9.977], p=0.016). Nonetheless, CAC was not associated with disease activity. Moreover, the extent of calcification score in TAK showed a positive correlation with the number of traditional cardiovascular risk factors. CONCLUSIONS: We recommend CCTA screening for Numano V classified TAK patients. Glucocorticoid usage significantly escalates the risk of CAC. Therefore, in cases of effectively controlled disease, the inclusion of immunosuppressants aimed at reducing glucocorticoid dosage is advisable.


Subject(s)
Computed Tomography Angiography , Coronary Angiography , Coronary Artery Disease , Takayasu Arteritis , Vascular Calcification , Humans , Takayasu Arteritis/diagnostic imaging , Takayasu Arteritis/epidemiology , Takayasu Arteritis/drug therapy , Takayasu Arteritis/complications , Female , Male , Retrospective Studies , Adult , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/epidemiology , Coronary Artery Disease/etiology , Vascular Calcification/diagnostic imaging , Vascular Calcification/epidemiology , Middle Aged , Risk Factors , Prevalence , Severity of Illness Index , Glucocorticoids/therapeutic use , Glucocorticoids/adverse effects , Young Adult , Heart Disease Risk Factors
8.
Inorg Chem ; 63(29): 13450-13458, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-38959430

ABSTRACT

The conversion of CO2 to generate high-value-added chemicals has become one of the hot research topics in green synthesis. Thereinto, the cyclization reaction of propargylic amines with CO2 is highly attractive because the resultant oxazolidinones are widely found in pharmaceutical chemistry. Cu(I)-based metal-organic frameworks (MOFs) as catalysts exhibit promising application prospects for CO2 conversion. However, their practical application was greatly limited due to Cu(I) being liable to disproportionation or oxidization. Herein, the solid copper(I) iodide thorium-based porous framework {[Cu5I6Th6(µ3-O)4(µ3-OH)4(H2O)10(L)10]·OH·4DMF·H2O}n (1) (HL = 2-methylpyridine-4-carboxylic acid) constructed by [Th6] clusters and [CuxIy] subunits was successfully prepared and structurally characterized. To our knowledge, this is the first copper(I) iodide-based actinide organic framework. Catalytic investigations indicate that 1 can effectively catalyze the cyclization of propargylic amines with CO2 under ambient conditions, which can be reused at least five times without a remarkable decline of catalytic activity. Importantly, 1 exhibits excellent chemical stability and the oxidation state of Cu(I) in it can remain stable under various conditions. This work can provide a valuable strategy for the synthesis of stable Cu(I)-MOF materials.

9.
Exp Cell Res ; 431(1): 113759, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37625768

ABSTRACT

Multiple myeloma (MM) is a B-cell malignancy characterized by the excessive proliferation of bone marrow plasma cells and the production of abnormal immunoglobulins. Despite advances in therapeutic strategies, it remains an incurable disease. Recently, innovative anticancer drugs have been developed and approved, leading to improvements in MM therapy; however, drug resistance continues to be a major obstacle that results in treatment failure. Therefore, the development of novel agents is imperative to achieve superior therapeutic outcomes for relapsed/refractory multiple myeloma (MM) patients. Previously, we identified EP12 as a c-Myc G4 stabilizer that could induce cytotoxicity in MM cells in vitro. However, further investigation is required to elucidate the underlying molecular mechanisms and anti-MM activity of EP12 in vivo. In this study, we have discovered that the compound EP12 effectively inhibits primary myeloma growth in vivo by destabilizing c-Myc and disrupting the canonical nuclear factor-κB (NF-κB) signaling pathway. Overall, our findings suggest that EP12, as a potent c-Myc inhibitor, holds great promise as a therapeutic agent for MM.


Subject(s)
Multiple Myeloma , NF-kappa B , Humans , NF-kappa B/genetics , Multiple Myeloma/drug therapy , Multiple Myeloma/genetics , Signal Transduction , B-Lymphocytes , Bone Marrow Cells
10.
Article in English | MEDLINE | ID: mdl-39078055

ABSTRACT

OBJECTIVE: This study aimed to analyze the pharmacokinetic (PK) characteristics, safety, and bioequivalence (BE) of a test (T) preparation of a nifedipine controlled-release tablet and the reference (R) drug (Adalat GTIS) in Chinese study participants in the context of fasting and postprandial states. MATERIALS AND METHODS: An open-label, single-center, randomized, single-dose, two-period study was designed including two separate arms, one with administration under fasting conditions and one with administration under postprandial conditions (high-fat, high-calorie breakfast). After oral administration, the nifedipine concentrations in plasma were quantitatively analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) at regular intervals. Primary PK parameters, including the area under the concentration curve from 0 to infinity (AUC0-∞), the area under the concentration profile from 0 to the last measurable concentration time (AUC0-t), and maximal measured plasma concentration (Cmax) were log-transformed with BE limits of 80 - 125% to evaluate BE. All adverse events (AEs) were wholly supervised. RESULTS: The PK profiles of the T and R formulations were comparable to each other under both fasting and postprandial conditions. The 90% confidence intervals (CIs) of the AUC0-∞, AUC0-t, and Cmax were 92.69 - 106.06%, 93.32 - 107.05%, and 99.53 - 116.71%, respectively, under the fasting state. The 90% CIs of the AUC0-∞, AUC0-t, and Cmax were 105.05 - 117.40%, 105.43 - 117.82%, and 102.66 - 116.30%, respectively, in the postprandial arm. 47 cases of drug-associated AEs were noted in the entire research. CONCLUSION: Under both the fasting and postprandial states, the two nifedipine controlled-release formulations were bioequivalent and safe in healthy Chinese subjects.

11.
BMC Public Health ; 24(1): 1625, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890613

ABSTRACT

OBJECTIVE: This study aimed to systematically review epidemiological evidence on associations between screen time exposure and myopia in children and adolescents, and to quantitatively evaluate summary effect estimates from existing literature. METHOD: There were three online databases including PubMed, Embase, and Web of Science, for epidemiological studies on screen time exposure and myopia published before June 1, 2023. The risk of bias was assessed by the Newcastle Ottawa Scale (NOS) checklist. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the correlation between screen time exposure and myopia using random or fixed-effect models by exposure type (categorical/continuous). We also performed subgroup analysis by screen device type, study quality, geographic region, and research period. RESULTS: We searched 7,571 records from three databases and identified 19 eligible studies, including 14 high-quality studies and 5 moderate-quality studies. Meta-analyses suggested that there was a statistically significant correlation between screen time (high vs. low) and myopia. The pooled ORs with 95%CIs were respectively 2.24 (1.47-3.42) for cross-sectional studies, and 2.39 (2.07-2.76) for cohort studies. We also found a significant association between continuous exposure to screen time (per 1 h/d increase) and myopia in cohort studies. The pooled ORs with 95%CIs were 1.07 (1.01-1.13). In subgroup analysis stratified by screen device type in cross-sectional studies, screen time exposures from computers (categorical: OR = 8.19, 95%CI: 4.78-14.04; continuous: OR = 1.22, 95%CI: 1.10-1.35) and televisions (categorical: OR = 1.46, 95%CI: 1.02-2.10) were associated with myopia, while smartphones were not. Although publication bias was detected, the pooled results did not show significant changes after adjustment using the trim and fill method. CONCLUSION: Our findings support that screen time exposure was significantly associated with myopia in children and adolescents. Notably, screen time exposure from computers may have the most significant impact on myopia.


Subject(s)
Myopia , Screen Time , Humans , Myopia/epidemiology , Child , Adolescent
12.
BMC Oral Health ; 24(1): 938, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39143610

ABSTRACT

BACKGROUND: Oral cancer is one of the most common cancers in China and seriously threaten life and health of Chinese people. We analysed the trends and disparities of oral cancer mortality rates and the disease burden of oral cancer in China from 2006 to 2021 to provide a reference for its prevention and control. METHODS: Annual death data for oral cancer was gleaned from the China Death Surveillance Database. The age-standardized mortality rate (ASMR), annual percentage change (APC), and average APC (AAPC) were used to analyze the trend of mortality. Loss of life expectancy (LLE) and years of life lost (YLL) were adopted to assess disease burden. RESULTS: From 2006 to 2021, the overall ASMR of oral cancer lightly declined (AAPC: - 0.97%; 95% CI: - 1.89%, - 0.04%), and the similar trend was observed among females (AAPC: - 1.22%; 95% CI: - 1.89%, - 0.55%). The ASMR of males was 2.31-3.16 times higher than that of females per year. The median of LLE for overall, males and females caused by oral cancer from 2006 to 2021 were 0.05, 0.06 and 0.03 years, respectively. There was a decrease of standardized YLL rate from 2006 to 2021 for overall (AAPC: - 1.31%, 95% CI: - 2.24% ~ - 0.37%) and for female (AAPC: - 1.63%, 95% CI: - 2.30% ~ - 0.95%). ASMR in urban areas was 1.02-1.28 times higher than that in rural areas from 2006 to2011, but 0.85-0.97 times lower in urban areas than that in rural areas from 2018 to 2021. The disease burden was higher in urban areas than in rural areas in 2006, whereas the reverse was observed in 2021. CONCLUSIONS: There are severe health gaps and disparities in trends between sexes and different areas in China. Males and rural populations need to be focused on targeted interventions for the main influencing factors.


Subject(s)
Cost of Illness , Life Expectancy , Mouth Neoplasms , Humans , China/epidemiology , Male , Mouth Neoplasms/mortality , Mouth Neoplasms/epidemiology , Female , Middle Aged , Life Expectancy/trends , Aged , Adult , Databases, Factual , Mortality/trends , Rural Population/statistics & numerical data , Population Surveillance , Aged, 80 and over
13.
J Environ Sci (China) ; 143: 201-212, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38644017

ABSTRACT

Silver (9 wt.%) was loaded on Co3O4-nanofiber using reduction and impregnation methods, respectively. Due to the stronger electronegativity of silver, the ratios of surface Co3+/Co2+ on Ag/Co3O4 were higher than on Co3O4, which further led to more adsorbed oxygen species as a result of the charge compensation. Moreover, the introducing of silver also obviously improved the reducibility of Co3O4. Hence the Ag/Co3O4 showed better catalytic performance than Co3O4 in benzene oxidation. Compared with the Ag/Co3O4 synthesized via impregnation method, the one prepared using reduction method (named as AgCo-R) exhibited higher contents of surface Co3+ and adsorbed oxygen species, stronger reducibility, as well as more active surface lattice oxygen species. Consequently, AgCo-R showed lowest T90 value of 183°C, admirable catalytic stability, largest normalized reaction rate of 1.36 × 10-4 mol/(h·m2) (150°C), and lowest apparent activation energy (Ea) of 63.2 kJ/mol. The analyzing of in-situ DRIFTS indicated benzene molecules were successively oxidized to phenol, o-benzoquinone, small molecular intermediates, and finally to CO2 and water on the surface of AgCo-R. At last, potential reaction pathways including five detailed steps were proposed.


Subject(s)
Benzene , Cobalt , Oxidation-Reduction , Oxides , Silver , Benzene/chemistry , Cobalt/chemistry , Silver/chemistry , Catalysis , Oxides/chemistry , Models, Chemical , Air Pollutants/chemistry
14.
Angew Chem Int Ed Engl ; 63(24): e202405676, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38606914

ABSTRACT

Metal-organic framework (MOF) membranes with rich functionality and tunable pore system are promising for precise molecular separation; however, it remains a challenge to develop defect-free high-connectivity MOF membrane with high water stability owing to uncontrollable nucleation and growth rate during fabrication process. Herein, we report on a confined-coordination induced intergrowth strategy to fabricate lattice-defect-free Zr-MOF membrane towards precise molecular separation. The confined-coordination space properties (size and shape) and environment (water or DMF) were regulated to slow down the coordination reaction rate via controlling the counter-diffusion of MOF precursors (metal cluster and ligand), thereby inter-growing MOF crystals into integrated membrane. The resulting Zr-MOF membrane with angstrom-sized lattice apertures exhibits excellent separation performance both for gas separation and water desalination process. It was achieved H2 permeance of ~1200 GPU and H2/CO2 selectivity of ~67; water permeance of ~8 L ⋅ m-2 ⋅ h-1 ⋅ bar-1 and MgCl2 rejection of ~95 %, which are one to two orders of magnitude higher than those of state-of-the-art membranes. The molecular transport mechanism related to size-sieving effect and transition energy barrier differential of molecules and ions was revealed by density functional theory calculations. Our work provides a facile approach and fundamental insights towards developing precise molecular sieving membranes.

15.
Mol Plant Microbe Interact ; 36(12): 779-795, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37551980

ABSTRACT

Fungal effectors play critical roles in manipulating plant immune responses and promoting colonization. Sphaerulina musiva is a heterothallic ascomycete fungus that causes Septoria leaf spot and stem canker disease in poplar (Populus spp.) plantations. This disease can result in premature defoliation, branch and stem breakage, increased mortality, and plantation failure. However, little is known about the interaction between S. musiva and poplar. Previous work predicted 142 candidate secreted effector proteins in S. musiva (SmCSEPs), 19 of which were selected for further functional characterization in this study. SmCSEP3 induced plant cell death in Nicotiana benthamiana, while 8 out of 19 tested SmCSEPs suppressed cell death. The signal peptides of these eight SmCSEPs exhibited secretory activity in a yeast signal sequence trap assay. Confocal microscopy revealed that four of these eight SmCSEPs target both the cytoplasm and the nucleus, whereas four predominantly localize to discrete punctate structures. Pathogen challenge assays in N. benthamiana demonstrated that the transient expression of six SmCSEPs promoted Fusarium proliferatum infection. The expression of these six SmCSEP genes were induced during infection. SmCSEP2, SmCSEP13, and SmCSEP25 suppressed chitin-triggered reactive oxygen species burst and callose deposition in N. benthamiana. The candidate secreted effector proteins of S. musiva target multiple compartments in the plant cell and modulate different pattern-triggered immunity pathways. [Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 "No Rights Reserved" license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2023.


Subject(s)
Ascomycota , Populus , Populus/genetics , Populus/microbiology , Virulence , Ascomycota/genetics , Plant Immunity , Plant Diseases/microbiology
16.
Plant Physiol ; 190(1): 459-479, 2022 08 29.
Article in English | MEDLINE | ID: mdl-35670753

ABSTRACT

Understanding gene expression and regulation requires insights into RNA transcription, processing, modification, and translation. However, the relationship between the epitranscriptome and the proteome under drought stress remains undetermined in poplar (Populus trichocarpa). In this study, we used Nanopore direct RNA sequencing and tandem mass tag-based proteomic analysis to examine epitranscriptomic and proteomic regulation induced by drought treatment in stem-differentiating xylem (SDX). Our results revealed a decreased full-length read ratio under drought treatment and, especially, a decreased association between transcriptome and proteome changes in response to drought. Epitranscriptome analysis of cellulose- and lignin-related genes revealed an increased N6-Methyladenosine (m6A) ratio, which was accompanied by decreased RNA abundance and translation, under drought stress. Interestingly, usage of the distal poly(A) site increased during drought stress. Finally, we found that transcripts of highly expressed genes tend to have shorter poly(A) tail length (PAL), and drought stress increased the percentage of transcripts with long PAL. These findings provide insights into the interplay among m6A, polyadenylation, PAL, and translation under drought stress in P. trichocarpa SDX.


Subject(s)
Populus , Droughts , Gene Expression Regulation, Plant , Populus/genetics , Populus/metabolism , Proteome/genetics , Proteome/metabolism , Proteomics , RNA/metabolism , Stress, Physiological/genetics , Xylem/genetics , Xylem/metabolism
17.
Cancer Cell Int ; 23(1): 27, 2023 Feb 15.
Article in English | MEDLINE | ID: mdl-36793075

ABSTRACT

BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in the biology of colorectal cancer (CRC). There are several lncRNAs associated with invasion and metastasis have been characterized in CRC. However, studies focusing on the precise molecular mechanisms by which lncRNAs function in lymph node (LN) metastasis in CRC are still limited. METHODS: In this study, by analyzing TCGA dataset, we identified that AC244100.2 (termed CCL14-AS), a novel lncRNA enriched in the cytoplasm, was negatively correlated with LN metastasis and unfavorable prognosis of CRC. In situ hybridization was used to examine CCL14-AS expression in clinical CRC tissues. Various functional experiments including migration assay and wound-healing assay were used to investigate the effects of CCL14-AS on CRC cells migration. The nude mice popliteal lymph node metastasis model assay further confirmed the effects of CCL14-AS in vivo. RESULTS: CCL14-AS expression was significantly downregulated in CRC tissues compared to adjacent normal tissues. In addition, low CCL14-AS expression was correlated with advanced T classification, LN metastasis, distant metastasis, and shorter disease-free survival of CRC patients. Functionally, CCL14-AS overexpression inhibited the invasiveness of CRC cells in vitro and LN metastasis in nude mice. On the contrary, knockdown of CCL14-AS promoted the invasiveness and LN metastasis abilities of CRC cells. Mechanistically, CCL14-AS downregulated the expression of MEP1A via interacting with MEP1A mRNA and reduced its stability. Overexpression of MEP1A rescued the invasiveness and LN metastasis abilities in CCL14-AS-overexpressing CRC cells. Moreover, the expression levels of CCL14-AS was negatively correlated with that of MEP1A in CRC tissues. CONCLUSIONS: We identified a novel lncRNA, CCL14-AS, as a potential tumor suppressor in CRC. Our findings supported a model in which the CCL14-AS/MEP1A axis serves as critical regulator in CRC progression, suggesting a novel biomarker and therapeutic target in advanced CRC.

18.
Exp Lung Res ; 49(1): 1-11, 2023.
Article in English | MEDLINE | ID: mdl-36420840

ABSTRACT

Background and aim: Pulmonary hypertension (PH) is a serious and even fatal disorder with limited treatment strategies. The hypoxia-induced pulmonary hypertension (HPH) rat model is commonly used in this field. While the HPH rat model has strong predictability and repeatability, the model is a chronic model, making it time-consuming, costly, and complicated and limiting the progress of the experiments. Currently, there is no uniform international standard for the HPH model. Our study aimed to find a relatively effective and efficient HPH modeling protocol. Methods: We established HPH rat models with different total hypoxia periods and different daily hypoxia times, and assessed different hypoxia modeling modes in multiple dimensions, such as haemodynamics, right ventricular (RV) hypertrophy, pulmonary arterial remodeling, muscularization, inflammation, and collagen deposition. Results: Longer daily hypoxia time resulted in higher mean pulmonary arterial pressure (mPAP)/right ventricular systolic pressure (RVSP) and more obvious RV hypertrophy, as well as more severe pulmonary arterial remodeling and muscularization, regardless of the total period of hypoxia (3- or 4-week). Moreover, pulmonary perivascular macrophages and collagen deposition showed daily hypoxia time-dependent increases, both in 3- and 4-week hypoxia groups. Conclusion: Our findings showed that the 3-week continuous hypoxia mode was a relatively efficient way to reduce the time needed to induce significant disease phenotypes, which offered methodological evidence for future studies in building HPH models.


Subject(s)
Hypertension, Pulmonary , Rats , Animals , Hypertension, Pulmonary/etiology , Vascular Remodeling , Hypoxia/complications , Hypertrophy, Right Ventricular/complications , Collagen , Pulmonary Artery
19.
Environ Res ; 237(Pt 1): 116987, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37633636

ABSTRACT

Efficiently addressing initial rainwater pollution is crucial for mitigating urban water pollution. However, the performance evaluation of initial rainwater pollution control project is rarely introduced. In this study, the architecture of effective comprehensive engineering measures for improving the water quality of initial rainwater in Anhui Province, China, was described. Three water quality indicators, ammonia nitrogen (NH3-N), chemical oxygen demand (COD), and total phosphorus (TP), were selected to explore the severity of urban pollution caused by initial rainwater under various rainfall scenarios. A single-factor evaluation method was used to contrast and assess the benefits of the initial rainfall interception project in terms of water quality enhancement. Results showed that initial rainfall pollution was gentler under light rainfall conditions but more prominent under moderate and heavy conditions. The percentages of NH3-N, COD, and TP in Lotus Pond that met the tertiary drinking water standard were 100%, 74.91%, and 100% with great improvement, and the average concentrations of NH3-N, COD, and TP in Fushan Road Drainage have decreased by 91.43%, 10.49%, and 57.33% respectively, after the construction of the interception project. These indicated that the nitrogen and phosphorus pollution were successfully controlled by the control techniques in both locations, but COD concentration has to be addressed with more specialized strategies. Overall, the water quality improvement project for initial rainwater pollution plays a great role in effectively governing initial rainwater pollution and improving river water quality, and provides an effective technical reference for urban water ecological environment management.

20.
Arch Toxicol ; 97(8): 2143-2153, 2023 08.
Article in English | MEDLINE | ID: mdl-37278767

ABSTRACT

While exposure to high levels of all-trans retinoic acid (atRA) during pregnancy is known to suppress murine embryonic palate mesenchymal (MEPM) cells proliferation and to result in cleft palate (CP) development, the underlying mechanisms are poorly understood. Accordingly, this study was designed with the goal of clarifying the etiological basis for atRA-induced CP. A murine model of CP was established via the oral administration of atRA to pregnant mice on gestational day (GD) 10.5, after which transcriptomic and metabolomic analyses were performed with the goal of clarifying the critical genes and metabolites associated with CP development through an integrated multi-omics approach. MEPM cells proliferation was altered by atRA exposure as expected, contributing to CP incidence. In total, 110 genes were differentially expressed in the atRA treatment groups, suggesting that atRA may influence key biological processes including stimulus, adhesion, and signaling-related activities. In addition, 133 differentially abundant metabolites were identified including molecules associated with ABC transporters, protein digestion and absorption, mTOR signaling pathway, and the TCA cycle, suggesting a link between these mechanisms and CP. Overall, combined analyses of these transcriptomic and metabolomic results suggested that the MAPK, calcium, PI3K-Akt, Wnt, and mTOR signaling pathways are particularly important pathways enriched in the palatal cleft under conditions of atRA exposure. Together, these integrated transcriptomic and metabolomic approaches provided new evidence with respect to the mechanisms underlying altered MEPM cells proliferation and signal transduction associated with atRA-induced CP, revealing a possible link between oxidative stress and these pathological changes.


Subject(s)
Cleft Palate , Pregnancy , Female , Animals , Mice , Cleft Palate/chemically induced , Cleft Palate/genetics , Cleft Palate/pathology , Transcriptome , Phosphatidylinositol 3-Kinases/metabolism , Tretinoin/toxicity , Cell Proliferation , TOR Serine-Threonine Kinases/metabolism , Mice, Inbred C57BL
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