A primary hallmark of pathological cardiac hypertrophy is excess protein synthesis due to enhanced translational activity. However, regulatory mechanisms at the translational level under cardiac stress remain poorly understood. Here we examined the translational regulations in a mouse cardiac hypertrophy model induced by transaortic constriction (TAC) and explored the conservative networks versus the translatome pattern in human dilated cardiomyopathy (DCM). The results showed that the heart weight to body weight ratio was significantly elevated, and the ejection fraction and fractional shortening significantly decreased 8 weeks after TAC. Puromycin incorporation assay showed that TAC significantly increased protein synthesis rate in the left ventricle. RNA-seq revealed 1,632 differentially expressed genes showing functional enrichment in pathways including extracellular matrix remodeling, metabolic processes, and signaling cascades associated with pathological cardiomyocyte growth. When combined with ribosome profiling analysis, we revealed that translation efficiency (TE) of 1,495 genes was enhanced, while the TE of 933 genes was inhibited following TAC. In DCM patients, 1,354 genes were upregulated versus 1,213 genes were downregulated at the translation level. Although the majority of the genes were not shared between mouse and human, we identified 93 genes, including Nos3, Kcnj8, Adcy4, Itpr1, Fasn, Scd1, etc., with highly conserved translational regulations. These genes were remarkably associated with myocardial function, signal transduction, and energy metabolism, particularly related to cGMP-PKG signaling and fatty acid metabolism. Motif analysis revealed enriched regulatory elements in the 5' untranslated regions (5'UTRs) of transcripts with differential TE, which exhibited strong cross-species sequence conservation. Our study revealed novel regulatory mechanisms at the translational level in cardiac hypertrophy and identified conserved translation-sensitive targets with potential applications to treat cardiac hypertrophy and heart failure in the clinic.
Animals ; Humans ; Cardiomegaly/physiopathology* ; Ribosomes/physiology* ; Protein Biosynthesis/physiology* ; Mice ; Cardiomyopathy, Dilated/genetics* ; Ribosome Profiling

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

In recent years, the spread of clubroot disease caused by Plasmodiophora brassicae infection has seriously affected the yield and quality of Brassica juncea (L.) Czern.. The cascade of mitogen-activated protein kinases (MAPKs), a highly conserved signaling pathway, plays an important role in plant responses to both biotic and abiotic stress conditions. To mine the MAPK genes related to clubroot disease resistance in B. juncea, we conducted a genome-wide analysis on this vegetable, and we analyzed the phylogenetic evolution and gene structure of the MAPK gene family in mustard. The 66 BjuMAPK genes identified by screening the whole genome sequence of B. juncea were unevenly distributed on 17 chromosomes. At the genomic scale, tandem repeats led to an increase in the number of MAPK genes in B. juncea. It was found that members of the same subfamily had similar gene structures, and there were great differences among different subfamilies. These predicted cis-acting elements were related to plant hormones, stress resistance, and plant growth and development. The expression of BjuMAPK02, BjuMAPK15, BjuMAPK17, and BjuMAPK19 were down-regulated or up-regulated in response to P. brassicae infection. The above results lay a theoretical foundation for further studying the functions of BjuMAPK genes in B. juncea in response to the biotic stress caused by clubroot disease.
Mustard Plant/parasitology* ; Plasmodiophorida/pathogenicity* ; Plant Diseases/genetics* ; Mitogen-Activated Protein Kinases/metabolism* ; Phylogeny ; Disease Resistance/genetics* ; Gene Expression Regulation, Plant ; Genome, Plant ; Plant Proteins/genetics*

Aim To establish and evaluate an alternative meth-od for detecting skin sensitization of cosmetics based on local lymph node assay using bromodeoxyuridine(BrdU)with flow cytometry(FCM).Methods(1)25％hexyl cinnamic alde-hyde(HCA)was chosen as a positive control with an acetone:olive oil(4∶1,V/V,AOO)mixture as a vehicle control for the experiment.The dorsal sides of both ears of mice were treated with test solutions on day 1,day 2,and day 3.Brdu solution was injected inter-peritoneally on day 5.On day 6,the bilateral ears and mandibular lymph nodes were excised,and the number of Brdu positive cells was measured by flow cytometry.The stim-ulation index(SI)was calculated to identify whether it was ≥3,in order to establish the method of LLNA:Brdu-FCM.(2)BrdU-FCM test was conducted using a blind method with the fif-teen reference substances listed in OECD TG429 whose skin sensitization potentials were known.The test substances were dissolved in AOO,N,N-dimethylformamide(DMF)or dimeth-yl sulfoxide(DMSO)at three different concentrations.Tests were performed the same as above.SI and EC2.7 were calculat-ed to evaluate whether the test substance was categorized as a skin sensitizer.The reliability and accuracy of the method were validated by comparing the classification of test substances with that in OECD TG429.Results The SI for 25％HCA was 3.9,showing positive in the skin sensitization test.It demonstrated that the LLNA:Brdu-FCM test method was properly implemen-ted.Nine test substances(2,4-dinitrochlorobenzene,4-pheny-lenediamine,cobalt chloride,2-mercaptobenzothiazole,hexyl-cinnamaldehyde,eugenol,phenyl benzoate,cinnamic alcohol,imidazolidinyl urea)were positive,and six test substances(methyl methacrylate,chlorobenzene,isopropanol,lactic acid,methyl salicylate,salicylic acid)were negative.The method was evaluated with sensitivity of 90％,specificity of 100％,positive prediction rate of 100％,negative prediction rate of 83％,false positive rate of 0％,false negative rate of 17％and accuracy of 93％.The LLNA:BrdU-FCM assay could correctly categorize the test substances that were skin sensitizers or non-sensitizers.Conclusion The LLNA:BrdU-FCM assay appears to be a relia-ble predictor of skin sensitization protential of chemicals,and it is expected to an alternative method for identifying skin sensitization as a supplementary in safety evaluation of cosmetic ingredient.

Aim To establish and evaluate an alternative meth-od for detecting skin sensitization of cosmetics based on local lymph node assay using bromodeoxyuridine(BrdU)with flow cytometry(FCM).Methods(1)25％hexyl cinnamic alde-hyde(HCA)was chosen as a positive control with an acetone:olive oil(4∶1,V/V,AOO)mixture as a vehicle control for the experiment.The dorsal sides of both ears of mice were treated with test solutions on day 1,day 2,and day 3.Brdu solution was injected inter-peritoneally on day 5.On day 6,the bilateral ears and mandibular lymph nodes were excised,and the number of Brdu positive cells was measured by flow cytometry.The stim-ulation index(SI)was calculated to identify whether it was ≥3,in order to establish the method of LLNA:Brdu-FCM.(2)BrdU-FCM test was conducted using a blind method with the fif-teen reference substances listed in OECD TG429 whose skin sensitization potentials were known.The test substances were dissolved in AOO,N,N-dimethylformamide(DMF)or dimeth-yl sulfoxide(DMSO)at three different concentrations.Tests were performed the same as above.SI and EC2.7 were calculat-ed to evaluate whether the test substance was categorized as a skin sensitizer.The reliability and accuracy of the method were validated by comparing the classification of test substances with that in OECD TG429.Results The SI for 25％HCA was 3.9,showing positive in the skin sensitization test.It demonstrated that the LLNA:Brdu-FCM test method was properly implemen-ted.Nine test substances(2,4-dinitrochlorobenzene,4-pheny-lenediamine,cobalt chloride,2-mercaptobenzothiazole,hexyl-cinnamaldehyde,eugenol,phenyl benzoate,cinnamic alcohol,imidazolidinyl urea)were positive,and six test substances(methyl methacrylate,chlorobenzene,isopropanol,lactic acid,methyl salicylate,salicylic acid)were negative.The method was evaluated with sensitivity of 90％,specificity of 100％,positive prediction rate of 100％,negative prediction rate of 83％,false positive rate of 0％,false negative rate of 17％and accuracy of 93％.The LLNA:BrdU-FCM assay could correctly categorize the test substances that were skin sensitizers or non-sensitizers.Conclusion The LLNA:BrdU-FCM assay appears to be a relia-ble predictor of skin sensitization protential of chemicals,and it is expected to an alternative method for identifying skin sensitization as a supplementary in safety evaluation of cosmetic ingredient.

Animals ; Macaca mulatta ; Optic Disk ; Glaucoma ; Craniocerebral Trauma ; Intraocular Pressure ; Low Tension Glaucoma

ObjectiveTo investigate the high-risk detection rate and aggregation of cardiovascular diseases（CVD） in 8 districts of Shanghai and influencing factors， and to provide scientific references for prevention and control of CVD. MethodsBased on the Cardiovascular Disease Screening and Management Program in Shanghai from 2016 to 2021， 104 685 participants aged 35 to 75 in 8 districts of Shanghai were selected for analysis. χ² test and multivariate logistic regression were used for statistical analysis of the influencing factors of CVD and aggregation of CVD. ResultsThe proportion of high-risk CVD individuals in the population was 19.17%， including the high-risk individuals with hypertension （8.65%）， dyslipidemia （6.33%）， CVD history （5.58%）， and WHO assessed risk ≥20% types （2.69%）， respectively. Old age， overweight and obesity， central obesity， smoking， drinking， farmers， unmarried， and low family income were the risk factors of CVD， while high education level was the protective factor. In the participants， 16 323 people （81.34%） were classified as CVD high-risk groups； The number of aggregation of 1， 2 and ≥3 high risk types of CVD were 16 323（81.34%）， 3 236（16.13%）， 509（2.54%）， respectively. Old age， low education level， low annual family income， farmers， unmarried， smoking， drinking， overweight， obesity and central obesity were associated with the risk of aggregation of high risk types of CVD， and the correlation strength increased with the increase of aggregation types. ConclusionThe prevention and control of CVD in Shanghai should focus on the hypertension， elderly， overweight， obesity， central obesity， smoking， drinking， low educated， low family income， farmers and unmarried people， and targeted intervention measures should be taken to reduce the risk of CVD among residents.

Objective To explore the role of resveratrol in the immune response and proliferation of macrophages induced by homocysteine(Hcy).Methods ANA-1 cells were divided into control group(conventional culture),model group(100 μmol·L-1 Hcy),experimental-L,-M,-H groups(adding 25,50 and 100 μmol·L-1 resveratrol to model group,respectively),Hcy+Ad-SIRT1 group(100 μmol·L-1 Hcy+Ad-SIRT1),Hcy+si-FOXO1 group(100 μmol·L-1 Hcy+si-FOXO1),Hcy+Res-L+Ad-SIRT1+si-FOXO1 group(100 μmol·L-1 Hcy+25 μmol·L-1 Resveratrol transfected with Ad-SIRT1+si-FOXO1).The cell proliferation was detected by methyl thiazolyl tetrazolium(MTT),and the concentration of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the supernatant of cell culture medium was detected by enzyme-linked immunosorbent assay.The gene and protein expression of silencing information regulator 1(SIRT1)and forkhead protein 01(FOXO1)were detected by Western blot.Results The optical density of 450 nm in control group,model group and experimental-L,-M,-H groups were 0.25±0.02,0.36±0.02,0.33±0.01,0.30±0.02 and 0.29±0.01,respectively.Compared with the control group,the cell proliferation in the model group was significantly increased(P＜0.05).Cell proliferation in experimental-L,-M,-H groups was significantly decreased compared with model group(all P＜0.05).IL-6 in the supernatant of cell culture medium of control group,model group and experimental-L group were(394.04±20.06),(614.23±21.09)and(501.53±16.52)pg·mL-1,respectively;TNF-α were(516.54±18.96),(717.22±24.81)and(632.74±19.11)pg·mL-1,respectively;SIRT1 relative protein expression were(1.00±0.05),(0.57±0.05)and(0.77±0.04),respectively;the relative protein expression of FOXO1 were 1.00±0.05,2.31±0.18 and 1.58±0.11,respectively.Compared with the control group,the above indexes in the experimental-L group had statistical significance(all P＜0.05).The contents of IL-6 and TNF-α in cell culture fluid supernatant in model group,experimental-L group,Hcy+Ad-SIRT1 group and Hcy+si-FOXO1 group were significantly lower than those in model group,with statistical significance(all P＜0.05).After co-transfection with Ad-SIRT1 and si-FOXO1,the contents of IL-6 and TNF-α in cell culture medium superserum of experimental-L group were significantly lower than those of Ad-SIRT1 group and si-FOXO1 group(all P＜0.05).Conclusion Resveratrol can attenuate the immune response and proliferation of macrophages induced by Hcy,which may be related to the alteration of SIRT1/FOXO1 pathway.