Di-n-butyl phthalate induces toxicity in male fetal mouse testicular development by regulating the MAPK signaling pathway.

"White pollution" has a significant impact on male reproduction. Di-n-butyl phthalate (DBP) is one of the most important factors in this type of pollution. Currently, research from international sources has demonstrated the significant reproductive toxicity of DBP. However, most of these studies have focused mainly on hormones expression at the protein and mRNA levels and the specific molecular targets of DBP and its mechanisms of action remain unclear. In this study, we established a Sprague Dawley pregnant mouse model exposed to DBP, and all male offspring were immediately euthanized at birth and bilateral testes were collected. We found through transcriptome sequencing that cell apoptosis and MAPK signaling pathway are the main potential pathways for DBP induced reproductive toxicity. Molecular biology analyses revealed a significant increase in the protein levels of JNK1(MAPK8) and BAX, as well as a significant increase in the BAX/BCL2 ratio after DBP exposure. Therefore, we propose that DBP induces reproductive toxicity by regulating JNK1 expression to activate the MAPK signaling pathway and induce reproductive cell apoptosis. In conclusion, our study provides the first evidence that the MAPK signaling pathway is involved in DBP-induced reproductive toxicity and highlights the importance of JNK1 as a potential target of DBP in inducing reproductive toxicity.

Rising Perfluorocyclobutane (PFC-318, c-C4F8) Emissions in China from 2011 to 2020 Inferred from Atmospheric Observations.

Global atmospheric emissions of perfluorocyclobutane (c-C4F8, PFC-318), a potent greenhouse gas, have increased rapidly in recent years. Combining atmospheric observations made at nine Chinese sites with a Lagrangian dispersion model-based Bayesian inversion technique, we show that PFC-318 emissions in China grew by approximately 70% from 2011 to 2020, rising from 0.65 (0.54-0.72) Gg year-1 in 2011 to 1.12 (1.05-1.19) Gg year-1 in 2020. The PFC-318 emission increase from China played a substantial role in the overall increase in global emissions during the study period, contributing 58% to the global total emission increase. This growth predominantly originated in eastern China. The regions with high emissions of PFC-318 in China overlap with areas densely populated with polytetrafluoroethylene (PTFE) factories, implying that fluoropolymer factories are important sources of PFC-318 emissions in China. Our investigation reveals an emission factor of approximately 3.02 g of byproduct PFC-318 emissions per kg of hydrochlorofluorocarbon-22 (HCFC-22) feedstock use in the production of tetrafluoroethylene (TFE) (for PTFE production) and hexafluoropropylene (HFP) if we assume all HCFC-22 produced for feedstock uses in China are pyrolyzed to produce PTFE and HFP. Further facility-level sampling and analysis are needed for a more precise evaluation of emissions from these factories.

Prevalence and genetic characteristics of fosB-positive Staphylococcus aureus in duck farms in Guangdong, China in 2020.

OBJECTIVES: To investigate the epidemiology of fosB-positive Staphylococcus aureus in waterfowl farms in the Pearl River tributaries in Guangdong Province, China in 2020. METHODS: A total of 63 S. aureus were recovered from 315 samples collected from six duck farms and one goose farm. PFGE, WGS and analysis were performed on 19 fosB-positive S. aureus. RESULTS: The fosfomycin resistance rate of the strains was as high as 52.4% (33/63), and 30.1% (19/63) of the strains carried fosB. Resistance gene prediction results showed that duck farm environment-derived strains contained the oxazolidinone drug resistance gene optrA. All fosB-positive S. aureus were MRSA and most of them were MDR, mainly ST9-t899 and ST164-t899. PFGE showed that fosB-positive S. aureus from humans and ducks could be clustered into the same clade. In addition, core-genome SNP analysis showed that clonal transmission of S. aureus occurred between humans and water. Pan-genome analysis showed that S. aureus had an open pangenome. The fosB gene was located on 2610-2615 bp plasmids, which all contained a broad host-range plasmid replication protein family 13. Small plasmids carrying the fosB gene could be found in different multilocus STs of S. aureus. CONCLUSIONS: This study indicated that duck farms in Guangdong, China could be an important reservoir of fosB-positive S. aureus. The spread of drug-resistant bacteria in waterfowl farms requires further monitoring.

Atmospheric Observation and Emission of HFC-134a in China and Its Four Cities.

1,1,1,2-Tetrafluoroethane (HFC-134a) is widely used as a refrigerant to replace dichlorodifluoromethane (CFC-12), and a small amount of it is used in the foam and medical aerosol sectors, with a high global warming potential and fast-increasing atmospheric concentration. The emission of HFC-134a in China has been growing at an average annual growth rate of 14.4% since 2009, reaching 53.0 (47.5-58.7) kt yr-1 in 2020. Among the five emission sources, emissions from the mobile air conditioning (MAC) sector accounted for the highest proportion of 65% on average of the total, followed by the commercial air conditioning (CAC) sector (25%), the medical aerosols sector (8%), the foam sector (2%), and leakage emission from the production (less than 0.1%). The emissions of HFC-134a in four cities in China (Beijing, Guangzhou, Hangzhou, and Lanzhou) were also estimated and discussed. Beijing had the highest HFC-134a emission of 2.2 kt yr-1 in 2020, and Lanzhou had the lowest emission of only 0.2 kt yr-1. In Beijing and Guangzhou, emissions from the CAC sector surpassed those from the MAC sector, becoming the most important source of HFC-134a. The average annual growth rate of HFC-134a's emissions during 2009-2019 was close to its concentration enhancement growth rate of 12.7%, and the emissions also showed significant correlations with the concentration enhancements in both China and four cities. This indicates the importance of the muti-city and long-term observations for the verification of HFC-134a's emission estimates at a regional scale.

Pathway and Cost-Benefit Analysis to Achieve China's Zero Hydrofluorocarbon Emissions.

Global hydrofluorocarbon (HFC) cumulative emissions will be more than 20 Gt CO2-equiv during 2020-2060 and have a non-negligible impact on global warming even in full compliance with the Kigali Amendment (KA). Fluorochemical manufacturers (including multinationals) in China have accounted for about 70% of global HFC production since 2015, of which about 60% is emitted outside China. This study built an integrated model (i.e., DECAF) to estimate both territorial and exported emissions of China under three scenarios and assess the corresponding climate effects as well as abatement costs. Achieving near-zero territorial emissions by 2060 could avoid 23 ± 4 Gt CO2-equiv of cumulative territorial emissions (compared to the 2019 Baseline scenario) during 2020-2060 at an average abatement cost of 9 ± 6 USD/t CO2-equiv. Under the near-zero emission (including territorial and abroad) pathway, radiative forcing from HFCs will peak in 2037 (60 ± 6 mW/m2) with a 33% peak reduction and 8 years in advance compared to the path regulated by the KA, and the radiative forcing by 2060 will be lower than that in 2019. Accelerated phase-out of HFC production in China could provide a possibility for rapid global HFC abatement and achieve greater climate benefits.

Inverse Modeling Revealed Reversed Trends in HCFC-141b Emissions for China during 2018-2020.

Having the highest ozone-depleting potential among hydrochlorofluorocarbons (HCFCs), the production and consumption of HCFC-141b (1,1-dichloro-1-fluoroethane, CH3CCl2F) are controlled by the Montreal Protocol. A renewed rise in global HCFC-141b emissions was found during 2017-2020; however, the latest changes in emissions across China are unclear for this period. This study used the FLEXible PARTicle dispersion model and the Bayesian framework to quantify HCFC-141b emissions based on atmospheric measurements from more sites across China than those used in previous studies. Results show that the estimated HCFC-141b emissions during 2018-2020 were on average 19.4 (17.3-21.6) Gg year-1, which was 3.9 (0.9-7.0) Gg year-1 higher than those in 2017 (15.5 [13.4-17.6] Gg year-1), showing a renewed rise. The proportion of global emissions that could not be exactly traced in 2020 was reduced from about 70% reported in previous studies to 46% herein. This study reconciled the global emission rise of 3.0 ± 1.2 Gg year-1 (emissions in 2020 - emissions in 2017): China's HCFC-141b emissions changed by 4.3 ± 4.5 Gg year-1, and the combined emissions from North Korea, South Korea, western Japan, Australia, northwestern Europe, and the United States changed by -2.2 ± 2.6 Gg year-1, while those from other countries/regions changed by 0.9 ± 5.3 Gg year-1.

Anthropogenic Chloroform Emissions from China Drive Changes in Global Emissions.

Emissions of chloroform (CHCl3), a short-lived halogenated substance not currently controlled under the Montreal Protocol on Substances that Deplete the Ozone Layer, are offsetting some of the achievements of the Montreal Protocol. In this study, emissions of CHCl3 from China were derived by atmospheric measurement-based "top-down" inverse modeling and a sector-based "bottom-up" inventory method. Top-down CHCl3 emissions grew from 78 (72-83) Gg yr-1 in 2011 to a maximum of 193 (178-204) Gg yr-1 in 2017, followed by a decrease to 147 (138-154) Gg yr-1 in 2018, after which emissions remained relatively constant through 2020. The changes in emissions from China could explain all of the global changes during the study period. The CHCl3 emissions in China were dominated by anthropogenic sources, such as byproduct emissions during disinfection and leakage from chloromethane industries. Had emissions continued to grow at the rate observed up to 2017, a delay of several years in Antarctic ozone layer recovery could have occurred. However, this delay will be largely avoided if global CHCl3 emissions remain relatively constant in the future, as they have between 2018 and 2020.

In Situ Observations of Halogenated Gases at the Shangdianzi Background Station and Emission Estimates for Northern China.

Halogenated gases include ozone-depleting substances and greenhouse gases, such as chlorofluorocarbons, halons, hydrochlorofluorocarbons, hydrofluorocarbons, and perfluorinated gases. In situ atmospheric observations of major halogenated gases were conducted at the Shangdianzi (SDZ) background station, China, from October 2020 to September 2021 using ODS5-pro, a newly developed measurement system. The measurement time series of 36 halogenated gases showed occasional pollution events, where background conditions represented 25% (CH2Cl2) to 81% (CF3Cl, CFC-13) of the measurements. The annual mean background mole fractions of most species at SDZ were consistent with those obtained at the Mace Head station in Ireland. The background conditions were distinguished from pollution events, and the enhanced mole fractions were used to estimate the emissions of four categories of fluorinated gases (F-gases) from northern China using a tracer ratio method. The CO2-equivalent (CO2-equiv) emission of F-gases from northern China reached 181 ± 18 Tg year-1 during 2020-2021. Among the four categories of F-gases estimated, SF6 accounted for the highest proportion of CO2-equiv emissions (24%), followed by HFC-23 (22%), HFC-125 (17%), HFC-134a (13%), NF3 (10%), CF4 (5.9%), HFC-143a (3.9%), HFC-32 (3.4%), and HFC-152a (0.2%).

Modulation of tissue repair by regeneration enhancer elements.

How tissue regeneration programs are triggered by injury has received limited research attention. Here we investigate the existence of enhancer regulatory elements that are activated in regenerating tissue. Transcriptomic analyses reveal that leptin b (lepb) is highly induced in regenerating hearts and fins of zebrafish. Epigenetic profiling identified a short DNA sequence element upstream and distal to lepb that acquires open chromatin marks during regeneration and enables injury-dependent expression from minimal promoters. This element could activate expression in injured neonatal mouse tissues and was divisible into tissue-specific modules sufficient for expression in regenerating zebrafish fins or hearts. Simple enhancer-effector transgenes employing lepb-linked sequences upstream of pro- or anti-regenerative factors controlled the efficacy of regeneration in zebrafish. Our findings provide evidence for 'tissue regeneration enhancer elements' (TREEs) that trigger gene expression in injury sites and can be engineered to modulate the regenerative potential of vertebrate organs.

Long-term outcomes of left bundle branch area pacing versus biventricular pacing in patients with heart failure and complete left bundle branch block.

Left bundle branch area pacing (LBBAP) has developed in an effort to improve cardiac resynchronization therapy (CRT). We aimed to compare the long-term clinical outcomes between LBBAP and biventricular pacing (BIVP) in patients with heart failure (HF) and complete left bundle branch block (CLBBB). Consecutive patients with HF and CLBBB requiring CRT received either LBBAP or BIVP were recruited at the Second Affiliated Hospital of Nanchang University from February 2018 to May 2019. We assessed their implant parameters, electrocardiogram (ECG), clinical outcomes at implant and during follow-up at 1, 3, 6, 12, and 24 months. Forty-one patients recruited including 21 for LBBAP and 20 for BIVP. Mean follow-up duration was 23.71 ± 4.44 months. LBBAP produced lower pacing thresholds, shorter procedure time and fluoroscopy duration compared to BIVP. The QRS duration was significantly narrower after LBBAP than BIVP (129.29 ± 31.46 vs. 156.85 ± 26.37 ms, p = 0.005). Notably, both LBBAP and BIVP significantly improved LVEF, LVEDD, NYHA class, and BNP compared with baseline. However, LBBAP significantly lowered BNP compared with BIVP (416.69 ± 411.39 vs. 96.07 ± 788.71 pg/ml, p = 0.007) from baseline to 24-month follow-up. Moreover, patients who received LBBAP exhibited lower number of hospitalizations than those in the BIVP group (p = 0.019). In addition, we found that patients with moderately prolonged left ventricular activation time (LVAT) and QRS notching in limb leads in baseline ECG respond better to LBBAP for CLBBB correction. LBBAP might be a relative safe and effective resynchronization therapy and as a supplement to BIVP for patients with HF and CLBBB.

Permanent Left Bundle Branch Area Pacing for High-Degree Atrioventricular Block in a 6-Year-Old Child with 2-Year Follow-Up.

The feasibility and safety of left bundle branch area pacing (LBBAP) used in pediatric patients with atrioventricular block (AVB) have not been well demonstrated. Currently, only several case reports for pediatric patients have been published since the advent of LBBAP, with 3 months to 1 year follow-up. Here, we present a case of LBBAP in a 6-year-old child with a high-degree AVB secondary to the transcatheter device closure of congenital ventricular septal defect. No procedure-related complications were observed, and the electrical parameters were stable at 2-year follow-up. Additionally, we performed a systematic literature review on pediatric patients with LBBAP. Fifteen cases were retrieved after systematically searching PubMed and Embase databases. No complications have been reported among these published cases. In conclusion, consistent with previous cases, our case with 2-year follow-up has demonstrated that LBBAP may be an alternative pacing modality from a very early age. However, given the limited evidence, the long-term outcomes of LBBAP in pediatric patients should be further investigated.

Topical delivery of pluronic F127/TPGS mixed micelles-based hydrogel loaded with glycyrrhizic acid for atopic dermatitis treatment.

OBJECTIVE: The purpose of this study was to develop pluronic F127/d-a-tocopheryl polyethylene glycol 1000 succinate mixed micelles-based hydrogel (MMs-gel) for topical delivery of glycyrrhizic acid (GL) to improve its skin permeability and atopic dermatitis (AD) treatment. SIGNIFICANCE: GL loaded MMs-gel (GL-MMs-gel) could be potentially used as a promising nanocarrier for the treatment of AD. METHODS: GL-MMs were prepared by thin film hydration method and then loaded into carbopol gel. The formulation of GL-MMs-gel was optimized by full factorial design and systematically characterized for drug content, pH, spreadability, in vitro drug release and percutaneous permeation, etc. The therapeutic effect of GL-MMs-gel was also investigated in AD-like skin lesion model in BALB/c mice and compared with GL solution-based gel (GL-sol-gel). RESULTS: Spherical GL-MMs with particle size of ∼30 nm were successfully incorporated into carbopol gel to form GL-MMs-gel with drug content of (98.80 ± 1.30) %, pH of 6.0 ± 0.08, and spreadability of (7.1 ± 0.2) cm. In vitro drug release profile of GL-MMs-gel exhibited a sustained-release behavior. The permeation flux for GL-MMs-gel (5.15 ± 0.33 µg/cm2/h) was significantly higher than that of GL-sol-gel (3.08 ± 0.34 µg/cm2/h) and GL-MMs-gel increased the accumulative amounts of GL in rats' skin 8.41 times than GL-sol-gel. The GL-MMs-gel was more effective than GL-sol-gel in suppressions of various AD symptoms including skin lesions, edema, high IgE levels, epidermal hyperplasia, and mast cell infiltration. CONCLUSION: All results revealed that MMs-gel could be a promising carrier for topical delivery of GL for the treatment of AD.

The N-Terminal Acetyltransferase Naa50 Regulates Arabidopsis Growth and Osmotic Stress Response.

N-terminal acetylation (Nt-acetylation) is one of the most common protein modifications in eukaryotes. The function of Naa50, the catalytic subunit of the evolutionarily conserved N-terminal acetyltransferase (Nat) E complex, has not been reported in Arabidopsis. In this study, we found that a loss of Naa50 resulted in a pleiotropic phenotype that included dwarfism and sterility, premature leaf senescence and a shortened primary root. Further analysis revealed that root cell patterning and various root cell properties were severely impaired in naa50 mutant plants. Moreover, defects in auxin distribution were observed due to the mislocalization of PIN auxin transporters. In contrast to its homologs in yeast and animals, Naa50 showed no co-immunoprecipitation with any subunit of the Nat A complex. Moreover, plants lacking Naa50 displayed hypersensitivity to abscisic acid and osmotic stress. Therefore, our results suggest that protein N-terminal acetylation catalyzed by Naa50 plays an essential role in Arabidopsis growth and osmotic stress responses.

Cooperative activation of cardiac transcription through myocardin bridging of paired MEF2 sites.

Enhancers frequently contain multiple binding sites for the same transcription factor. These homotypic binding sites often exhibit synergy, whereby the transcriptional output from two or more binding sites is greater than the sum of the contributions of the individual binding sites alone. Although this phenomenon is frequently observed, the mechanistic basis for homotypic binding site synergy is poorly understood. Here, we identify a bona fide cardiac-specific Prkaa2 enhancer that is synergistically activated by homotypic MEF2 binding sites. We show that two MEF2 sites in the enhancer function cooperatively due to bridging of the MEF2C-bound sites by the SAP domain-containing co-activator protein myocardin, and we show that paired sites buffer the enhancer from integration site-dependent effects on transcription in vivo Paired MEF2 sites are prevalent in cardiac enhancers, suggesting that this might be a common mechanism underlying synergy in the control of cardiac gene expression in vivo.

The efficacy of remote ischemic conditioning in preventing contrast-induced nephropathy among patients undergoing coronary angiography or intervention: An updated systematic review and meta-analysis.

BACKGROUND: Numerous trials have investigated the effect of remote ischemic conditioning (RIC) in preventing contrast-induced nephropathy (CIN) in patients receiving contrast medium (CM). This meta analysis aims to validate the role of RIC in preventing CIN. METHODS: We searched the PubMed, EMBASE, and Web of Science databases for eligible randomized controlled trials (RCTs) published before April 27, 2019. Two investigators independently extracted basic characteristics from each study. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to examine the treatment effect. RESULTS: A total of 18 studies comprising 2,503 patients were included in our meta-analysis. Compared with conventional therapy, RIC significantly reduced the risk of CIN (OR = 0.43, 95% CI: 0.33, 0.56, p < .05). Subgroup analyses showed that the protective effect of RIC was stronger in the low-osmolar contrast media group (OR = 0.32; 95% CI: 0.23, 0.45, p < .05) and the nondiabetic group (OR = 0.39; 95% CI: 0.29, 0.53 p < .05). RIC also significantly reduced major adverse cardiovascular events within the first 6 months (OR = 0.39; p < .05), but the influence was not present after long-term follow-up. CONCLUSIONS: Our meta-analysis showed that RIC could effectively reduce CIN risk and decrease the short-term incidence of relevant adverse events. Furthermore, the effects of CIN are more pronounced in nondiabetic patients and with the use of low-osmolar contrast medium. This meta-analysis of small trials suggests a possible protective effect of RIC on contrast-induced nephropathy and favors the performance of a large randomized trial to further investigate this strategy.

Chronic exposure to di-n-butyl phthalate causes reproductive toxicity in zebrafish.

Di-n-butyl phthalate (DBP) is known to have adverse effects on reproduction in mammals and is pervasive in the aquatic environment. The objective of the present study was to investigate whether long-term exposure to low concentrations of DBP can affect fish reproduction. In this study, zebrafish (Danio rerio) embryos (F0 ) were exposed to low concentrations (4.9, 13.6 and 43.8 µg/L) of DBP from 2 hours post-fertilization until sexual maturation. The results demonstrate that chronic exposure to DBP (43.8 µg/L) impaired the reproductive function of zebrafish, as verified by reduced egg production and modifications to gonadal histology of the treated fish. Plasma 17ß-estradiol levels in female zebrafish decreased significantly in a concentration-dependent manner, while testosterone levels in males increased significantly when fish were exposed to 43.8 µg/L DBP. Real-time polymerase chain reaction was performed to examine selected genes in the hypothalamic-pituitary-gonadal (HPG) axis and liver. Hepatic vitellogenin gene transcription was downregulated in both males and females, suggesting that DBP possesses anti-estrogenic activity. The disturbed steroid hormones were accompanied by the significant alterations in gene expression along the HPG axis. Additionally, parental exposure to DBP caused reduced hatching and survival rate as well as decreased growth in the F1 generation. Taken together, these results demonstrate that long-term exposure to low concentrations of DBP in zebrafish could cause reproductive toxicity, implying that DBP could have significant adverse effects on fish populations, particularly in a highly DBP-contaminated aquatic environment.

The Prognostic Significance of EIF3C Gene during the Tumorigenesis of Prostate Cancer.

Prostate cancer (PCa) is the most common malignant tumor for men. But the mechanism is unclear. EIF3C was shown to be overexpressed in PCa tissues and cell lines. EIF3C overexpression was correlated to age and tumor stage in PCa patients and indicated poor survival. The proliferation, migration, and invasiveness of PC3 cells were all inhibited after EIF3C knockdown. Additionally, the phosphorylation level of PI3K and Akt was downregulated while total NF-κB and Myc decreased after EIF3C knockdown. But the expression of IκB increased reversely. Therefore, EIF3C at least partially regulates the activity of PI3K/Akt/NF-κB signaling pathway in PC3 cells.

Activation and allosteric modulation of a muscarinic acetylcholine receptor.

Despite recent advances in crystallography and the availability of G-protein-coupled receptor (GPCR) structures, little is known about the mechanism of their activation process, as only the ß2 adrenergic receptor (ß2AR) and rhodopsin have been crystallized in fully active conformations. Here we report the structure of an agonist-bound, active state of the human M2 muscarinic acetylcholine receptor stabilized by a G-protein mimetic camelid antibody fragment isolated by conformational selection using yeast surface display. In addition to the expected changes in the intracellular surface, the structure reveals larger conformational changes in the extracellular region and orthosteric binding site than observed in the active states of the ß2AR and rhodopsin. We also report the structure of the M2 receptor simultaneously bound to the orthosteric agonist iperoxo and the positive allosteric modulator LY2119620. This structure reveals that LY2119620 recognizes a largely pre-formed binding site in the extracellular vestibule of the iperoxo-bound receptor, inducing a slight contraction of this outer binding pocket. These structures offer important insights into the activation mechanism and allosteric modulation of muscarinic receptors.

Endothelin signaling activates Mef2c expression in the neural crest through a MEF2C-dependent positive-feedback transcriptional pathway.

Endothelin signaling is essential for neural crest development, and dysregulated Endothelin signaling is associated with several neural crest-related disorders, including Waardenburg and other syndromes. However, despite the crucial roles of this pathway in neural crest development and disease, the transcriptional effectors directly activated by Endothelin signaling during neural crest development remain incompletely elucidated. Here, we establish that the MADS box transcription factor MEF2C is an immediate downstream transcriptional target and effector of Endothelin signaling in the neural crest. We show that Endothelin signaling activates Mef2c expression in the neural crest through a conserved enhancer in the Mef2c locus and that CRISPR-mediated deletion of this Mef2c neural crest enhancer from the mouse genome abolishes Endothelin induction of Mef2c expression. Moreover, we demonstrate that Endothelin signaling activates neural crest expression of Mef2c by de-repressing MEF2C activity through a Calmodulin-CamKII-histone deacetylase signaling cascade. Thus, these findings identify a MEF2C-dependent, positive-feedback mechanism for Endothelin induction and establish MEF2C as an immediate transcriptional effector and target of Endothelin signaling in the neural crest.

Impacts of the Degradation of 2,3,3,3-Tetrafluoropropene into Trifluoroacetic Acid from Its Application in Automobile Air Conditioners in China, the United States, and Europe.

HFO-1234yf (2,3,3,3-tetrafluoropropene) was proposed as an automobile air conditioner (MAC) refrigerant worldwide. However, its atmospheric degradation product is the highly soluble and phytotoxic trifluoroacetic acid (TFA), which persists in aquatic environments. We used a global three-dimensional chemical transport model to assess the potential environmental effects resulting from complete future conversion of the refrigerant in all MAC to HFO-1234yf in China, the United States, and Europe. The annual mean atmospheric concentrations of HFO-1234yf were 2.62, 2.20, and 2.73 pptv, and the mean deposition rates of TFA were 0.96, 0.45, and 0.52 kg km-2 yr-1, in three regions. The regional TFA deposition sources mainly came from emissions within the same region. The annual TFA deposition in the North Pole region was lower than the global average and mainly originated from European emissions. A potential doubling in the future HFO-1234yf emissions in China mainly affected the local TFA depositions. The TFA concentrations in rainwater were strongly affected by the regional precipitation rates. North Africa and the Middle East, regions with scant rainfall, had extremely high TFA concentrations. The rainwater concentrations of TFA during individual rain events can exceed the level considered to be safe, indicating substantial potential regional risks from future HFO-1234yf use.