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The association between plasma low-density lipoprotein cholesterol (LDL-C) and atrial fibrillation (AF) recurrence after catheter ablation remains unclear. We aimed to assess the relationship between preprocedural LDL-C and the AF recurrence in patients undergoing catheter ablation. The cohort study consecutively included AF patients who underwent de novo catheter ablation between April 2021 and January 2023 in the Second Affiliated Hospital of Nanchang University in Jiangxi Province, China. Patients were divided into quartiles based on their baseline fasting LDL-C level (Q1-Q4). Multivariable Cox proportional hazards models were used to evaluate the relationship between LDL-C and AF recurrence. Our analysis included the use of a generalized additive model and smooth curve fitting (penalized spline method), and two-piecewise Cox proportional hazards models, to address the nonlinearity between preprocedural LDL-C and AF recurrence. A total of 482 AF patients with de novo catheter ablation were enrolled, with a median follow-up period of 15.00 months, AF recurrence occurred in 96 (19.92%) patients. The relationship between preprocedural LDL-C and AF recurrence after ablation presented as an L-shape, and the inflection point for the curve was found at the LDL-C level of 3.20 mmol/L (Log likelihood ratio P = 0.031). The hazard ratios (HR) [(95% confidence intervals (CI)] for AF recurrence were 0.50 (0.33-0.74) and 2.11 (0.76-5.89) to the left and right of the inflection point, respectively. Lower LDL-C level is associated with increased AF recurrence risk after catheter ablation were consistent across all subgroups., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

HFC-125 and HFC-32 are fluorinated greenhouse gases of great concern due to their high GWPs and increasing background atmospheric concentrations. Long-term atmospheric observations of HFC-125 and HFC-32 were carried out in four representative cities of China (Beijing, Guangzhou, Hangzhou, and Lanzhou) from January 2012 to October 2019. Overall, the annual mean atmospheric concentrations of HFC-125 and HFC-32 both showed increasing trends, with average rates of 4.8 ppt yr -1 and 7.9 ppt yr -1 . The average concentrations of HFC-125 and HFC-32 in urban areas were significantly higher than those in suburban areas. Significant differences in atmospheric concentrations of the two HFCs were observed among the four cities. HFC-125 and HFC-32 emissions were estimated accordingly, averaging 6.2 Gg yr -1 (23.6 Mt. CO 2 -eq) and 5.7 Gg yr -1 (4.3 Mt. CO 2 -eq) during 2012 and 2019 and growing at rates of 0.8 Gg yr -1 (3.1 Mt. CO 2 -eq) and 0.8 Gg yr -1 (0.6 Mt. CO 2 -eq), respectively, with an increasing contribution to global radiative forcing. The bottom-up inventories of HFC-125 and HFC-32 in the four cities increased annually from 2012 to 2019, with the highest emissions in Beijing, while the top-down emissions fluctuated during the research period. SYNOPSIS: The atmospheric concentrations of HFC-125 and HFC-32 were measured from 2012 to 2019 in four representative cities of China. Both HFC emissions at national and city levels were estimated using observation-based and inventory methods., Competing Interests: Declaration of competing interest The authors declare that they have no relevant financial or non-financial interests that could be construed as potential conflicts of interest with respect to the research, authorship, and/or publication of this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study explores the potential of synergistically reducing direct (refrigerant) and indirect (electricity) greenhouse gas (GHG) emissions in the global room air conditioning (RAC) sector, based on 80% of global RAC manufactured in China. Three scenarios are evaluated: Business-as-usual (BAU) based on maintaining refrigerant and energy efficiency levels from 2021 China RAC sales shares, Kigali Amendment compliant with 10% energy efficiency improvement by 2025 (KAE), and accelerated refrigerant transition and energy efficiency improvement (ATE). Each scenario considers the costs of refrigerant and efficiency measures for export market groups based on Kigali Amendment classifications. BAU predicts around 1 Gt CO 2 -eq average annual global RAC emissions (2022-2060). Cumulative emission reductions in China's RAC manufacturing under KAE and ATE are 12.2 and 17.2 Gt CO 2 -eq A5II and A5I (except China), presenting cost-effective abatement measures, with average costs of -$51.4 and -$68.8/t CO 2 -eq in KAE and ATE. Cumulative average abatement costs are around $18 and $4/t CO 2 -eq globally. KAE and ATE scenarios would avoid surface temperature rises of 0.023 (±0.002) °C and 0.027 (±0.003) °C, respectively, versus BAU. Collaboration between China and importing countries is urged to enhance energy efficiency in RACs traded, ensuring sustainable mitigation aligned with the Kigali Amendment.

In 2018, China implemented the Veterinary Antimicrobial Use Reduction Action to curb the rapid development of antibiotic resistance (AR). However, the AR-related pollutions in animal farms after the reduction policy has been poorly investigated. Here, we performed a comprehensive investigation combining UPLC-MS/MS, metagenomic, and bacterial genomic analyses in eight representative large-scale chicken farms in Guangdong, China. Our results showed that antibiotics and ARGs contaminations were more severe in broiler farms than in layer farms. Notably, diverse tet(X) variants were prevalent in the chicken farms. These tet(X)s was carried by diverse E. coli lineages and obviously correlated with ISCR2 and IS1B transposases. The resistomes in chicken farms was significantly correlated with microbial community, and multiple factor analyses indicated that the joint effect of antibiotics-microbial community-MGEs was the most dominant driver of ARGs. Host tracking identified a variety of ARG bacterial hosts and the co-occurrence of ARGs-MRGs-MGEs. Source tracking indicated that the inherent component represented the main feature of resistomes in different hosts, while ARG transfer between the chicken gut and farm environments were frequent. A multiperspective evaluation of AR risk revealed that the early effect of antibiotic reduction was exhibited by the mitigation of maximum level of risky ARGs, prevalence of environmental AR pathogens, and HGT potential of ARGs mediated by phage structures. Overall, our findings provide insights into the antibiotic and ARG profiles in large-scale chicken farms with different rearing strategies and demonstrate a preliminary view of the performance of antibiotic reduction actions in China., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The perfluorocarbons tetrafluoromethane (CF 4 , PFC-14) and hexafluoroethane (C 2 F 6 , PFC-116) are potent greenhouse gases with near-permanent atmospheric lifetimes relative to human timescales and global warming potentials thousands of times that of CO 2 . Using long-term atmospheric observations from a Chinese network and an inverse modeling approach (top-down method), we determined that CF 4 emissions in China increased from 4.7 (4.2-5.0, 68% uncertainty interval) Gg y -1 in 2012 to 8.3 (7.7-8.9) Gg y -1 in 2021, and C 2 F 6 emissions in China increased from 0.74 (0.66-0.80) Gg y -1 in 2011 to 1.32 (1.24-1.40) Gg y -1 in 2021, both increasing by approximately 78%. Combined emissions of CF 4 and C 2 F 6 in China reached 78 Mt CO 2 -eq in 2021. The absolute increase in emissions of each substance in China between 2011-2012 and 2017-2020 was similar to (for CF 4 ), or greater than (for C 2 F 6 ), the respective absolute increase in global emissions over the same period. Substantial CF 4 and C 2 F 6 emissions were identified in the less-populated western regions of China, probably due to emissions from the expanding aluminum industry in these resource-intensive regions. It is likely that the aluminum industry dominates CF 4 emissions in China, while the aluminum and semiconductor industries both contribute to C 2 F 6 emissions. Based on atmospheric observations, this study validates the emission magnitudes reported in national bottom-up inventories and provides insights into detailed spatial distributions and emission sources beyond what is reported in national bottom-up inventories., Competing Interests: Competing interests statement:The authors declare no competing interest.

Global atmospheric emissions of perfluorocyclobutane ( c -C 4 F 8 , 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.

Autosomal Recurrent Primary Microscopic (MCPH, OMIM: 251200) is a neurodevelopmental disorder that is characterized by a noticeable decrease in brain size, particularly in the cerebral cortex, but with a normal brain structure and a non-progressive intellectual disability. MCPH1 has been identified as the gene that triggers primary microcephaly (MCPH1，OMIM: 607117). Here we report a case of autosomal recessive primary microcephaly as caused by a novel variant in the MCPH1 gene. Head circumference was measured by Magnetic Resonance Imaging (MRI), while the Wechsler Intelligence Scale was used to evaluate the intelligence of the individual being tested. B-ultrasound was used to assess gonadal development, and semen routine was used to assess sperm status. The whole-exome sequencing (WES) was performed on the proband. Sanger sequencing was conducted on the parents of the proband to determine if the novel variant in the MCPH1 gene was present. The effect of the mutation on the splicing of MCPH1 was verified by minigene approach. It was observed that the proband had autosomal recessive primary microcephaly and azoospermatism. A novel splice-site homozygous mutation (c.233+2T > G) of the MCPH1 gene was identified, which inherited from his parents. Minigene approach confirmed that c.233+2T > G could affect the splicing of MCPH1 . Therefore, our findings contributed to the mutation spectrum of the MCPH1 gene and may be useful in the diagnosis and gene therapy of MCPH., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

"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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jianxin Hu reports financial support was provided by Science and Technology Program of Guizhou Province. Heng Luo reports financial support was provided by Science and Technology Program of Guizhou Province. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Sulfur hexafluoride (SF 6 ) is a potent greenhouse gas. Here we use long-term atmospheric observations to determine SF 6 emissions from China between 2011 and 2021, which are used to evaluate the Chinese national SF 6 emission inventory and to better understand the global SF 6 budget. SF 6 emissions in China substantially increased from 2.6 (2.3-2.7, 68% uncertainty) Gg yr -1 in 2011 to 5.1 (4.8-5.4) Gg yr -1 in 2021. The increase from China is larger than the global total emissions rise, implying that it has offset falling emissions from other countries. Emissions in the less-populated western regions of China, which have potentially not been well quantified in previous measurement-based estimates, contribute significantly to the national SF 6 emissions, likely due to substantial power generation and transmission in that area. The CO 2 -eq emissions of SF 6 in China in 2021 were 125 (117-132) million tonnes (Mt), comparable to the national total CO 2 emissions of several countries such as the Netherlands or Nigeria. The increasing SF 6 emissions offset some of the CO 2 reductions achieved through transitioning to renewable energy in the power industry, and might hinder progress towards achieving China's goal of carbon neutrality by 2060 if no concrete control measures are implemented., (© 2024. The Author(s).)

Introduction. Trichophyton rubrum is a major causative agent of superficial dermatomycoses such as onychomycosis and tinea pedis. Huangqin decoction (HQD), as a classical traditional Chinese medicine formula, was found to inhibit the growth of common clinical dermatophytes such as T. rubrum in our previous drug susceptibility experiments. Hypothesis/Gap Statement. The antifungal activity and potential mechanism of HQD against T. rubrum have not yet been investigated. Aim. The aim of this study was to investigate the antifungal activity and explore the potential mechanism of action of HQD against T. rubrum . Methodology. The present study was performed to evaluate the antifungal activity of HQD against T. rubrum by determination of minimal inhibitory concentrations (MICs), minimal fungicidal concentrations (MFCs), mycelial growth, biomass, spore germination and structural damage, and explore its preliminary anti-dermatophyte mechanisms by sorbitol and ergosterol assay, HPLC-based ergosterol test, enzyme-linked immunosorbent assay and mitochondrial enzyme activity test. Results. HQD was able to inhibit the growth of T. rubrum significantly, with an MIC of 3.125 mg ml -1 and an MFC of 12.5 mg ml -1 . It also significantly inhibited the hyphal growth, conidia germination and biomass growth of T. rubrum in a dose-dependent manner, and induced structural damage in different degrees for T. rubrum cells. HQD showed no effect on cell wall integrity, but was able to damage the cell membrane of T. rubrum by interfering with ergosterol biosynthesis, involving the reduction of squalene epoxidase (SE) and sterol 14α-demethylase P450 (CYP51) activities, and also affect the malate dehydrogenase (MDH), succinate dehydrogenase (SDH) and ATPase activities of mitochondria. Conclusion. These results revealed that HQD had significant anti-dermatophyte activity, which was associated with destroying the cell membrane and affecting the enzyme activities of mitochondria.

Background: Pulsed field ablation (PFA) has emerged as a novel non-thermal modality with highly myocardium-specific. However, the PFA catheter based on contact force (CF)-sensing has not been reported. The study aimed to evaluate the efficacy and safety of a novel CF-sensing PFA catheter., Methods: First, different CF (5, 15, 25, and 35 g) of the novel PFA catheter were evaluated on lesion dimensions during ablation on right and left ventricle in two pigs. Next, this catheter was further evaluated on four typical sites of superior vena cava (SVC), cavotricuspid isthmus (CTI), right superior pulmonary vein (RSPV), and right inferior pulmonary vein (RIPV) for atrial ablation in another six pigs. Electrical isolation was evaluated immediately after ablation and 30-day survival. Chronic lesions were assessed via histopathology after euthanasia. Acute and chronic safety outcomes were observed peri- and post-procedurally., Results: In ventricular ablation, increased CF from 5 to 15 g produced significantly greater lesion depth but nonsignificant increases from 15 to 35 g. In atrial ablation, the novel CF-sensing PFA deliveries produced an acute attenuation of local electrograms and formation of a continuous line of block in all 6 pigs. The ablation line remained sustained blockage at the 30-day survival period. The CF of SVC, CTI, RSPV, and RIPV was 9.4 ± 1.5, 14.5 ± 3.2, 17.2 ± 2.6, and 13.4 ± 2.8 g, respectively. Moreover, no evidence of damage to esophagus or phrenic nerve was observed., Conclusion: The novel CF-sensing PFA catheter potentiated efficient, safe, and durable ablation, without causing damage to the esophagus or phrenic nerve., (© 2024 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Having the highest ozone-depleting potential among hydrochlorofluorocarbons (HCFCs), the production and consumption of HCFC-141b (1,1-dichloro-1-fluoroethane, CH 3 CCl 2 F) 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 .

Immunotherapy of acute myeloid leukemia (AML) has been challenging because the lack of tumor-specific antigens results in "on-target, off-tumor" toxicity. To unlock the full potential of AML therapies, we used CRISPR-Cas9 to genetically ablate the myeloid protein CD33 from healthy donor hematopoietic stem and progenitor cells (HSPCs), creating tremtelectogene empogeditemcel (trem-cel). Trem-cel is a HSPC transplant product designed to provide a reconstituted hematopoietic compartment that is resistant to anti-CD33 drug cytotoxicity. Here, we describe preclinical studies and process development of clinical-scale manufacturing of trem-cel. Preclinical data showed proof-of-concept with loss of CD33 surface protein and no impact on myeloid cell differentiation or function. At clinical scale, trem-cel could be manufactured reproducibly, routinely achieving >70% CD33 editing with no effect on cell viability, differentiation, and function. Trem-cel pharmacology studies using mouse xenograft models showed long-term engraftment, multilineage differentiation, and persistence of gene editing. Toxicology assessment revealed no adverse findings, and no significant or reproducible off-target editing events. Importantly, CD33-knockout myeloid cells were resistant to the CD33-targeted agent gemtuzumab ozogamicin in vitro and in viv o. These studies supported the initiation of the first-in-human, multicenter clinical trial evaluating the safety and efficacy of trem-cel in patients with AML (NCT04849910)., Competing Interests: J.R.L., M.I.L., H.G.G., A.H., S.W., M.B.J., J.E., G.A., J.X.F., J.L., K.S., Y.K., H.M., J.S., J.H., and T.C. are salaried employees of Vor Biopharma Inc. and hold equity interests in the company. J.R.L., M.L., M.B.J., J.E., J.L., J.S., and T.C. are inventors on patent applications assigned to Vor Biopharma Inc. S.M. is a coinventor on patent applications related to this work, which were filed by Columbia University and are licensed to Vor Biopharma Inc. S.M. has equity ownership and is on the Scientific Advisory Board of Vor Biopharma Inc., (© 2023 VOR BIOPHARMA INC.)

Objectives: Staphylococcus aureus is an opportunistic pathogen that is considered a high priority for research. However, comparative studies of S. aureus strains from different environments and hosts are still lacking., Methods: Here, we performed a high-resolution bioinformatics analysis of 576 S. aureus genomes isolated from livestock, farm environments, farm workers, animal-origin food, and humans., Results: The S. aureus isolates showed high diversity in genetic lineages and demonstrated host specialization and multi-host range in the population phylogeny. Recent transmission events, historical divergences, and frequent host switching in specific sequence types (STs) and through the food chain and animal farm mediums were observed. Frequent gene transfer may quickly give rise to new fitness to colonize their host or switch to other hosts, even in isolates with the closest vertical evolutionary history. The large multi-host-shared antibiotic resistance gene (ARG) pool was the major factor shaping antibiotic resistance in S. aureus isolates. We revealed the genetic backgrounds of mec, cfr, and optrA, which could be spread among isolates from different species, hosts, and environments., Conclusion: Overall, our findings provide One Health genomic insights into the evolution, transmission, gene content characteristics, and antibiotic resistance profiles of S. aureus from different hosts, suggesting that, despite well-formed host specificity during the evolution of S. aureus, the ever-expanding host range and the cross-hosts/niches transmission (at both the strain and genetic level) may be facilitated by diverse bacterial vehicles (e.g., food chain, farm environments, and workers), which will lead to emerging antibiotic resistance consequences and threaten public health and food safety., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Emissions of chloroform (CHCl 3 ), 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 CHCl 3 from China were derived by atmospheric measurement-based "top-down" inverse modeling and a sector-based "bottom-up" inventory method. Top-down CHCl 3 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 CHCl 3 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 CHCl 3 emissions remain relatively constant in the future, as they have between 2018 and 2020.

Ozone-depleting substances (ODSs), which also contribute to global warming, have been controlled by the Montreal Protocol (MP) since 1987. China joined the MP in 1991 and began reducing production and consumption of ODSs in the country, leading to a decrease in emissions of ODSs. Based on the Intergovernmental Panel on Climate Change guidelines, the latest emission factors and actual consumption in China (MP scenario), both the historical banks and the historical emissions of ODSs and substitute hydrofluorocarbons (HFCs) during 1980-2020 were calculated. To understand the reduction in ODS and HFC emissions by implementing the MP, we also estimated China's virtual emissions (NMP, i.e., the amount of ODS emissions without the MP) over the same period. The avoided cumulative ODS consumption and emission values of 10.8 and 5.8 (4.8-6.9) million tonnes (Mt) of CFC-11-equivalent (eq), respectively, were estimated by comparing the two scenarios. Furthermore, 26 (22-33) giga tonnes (Gt) of CO 2 -eq emissions, equivalent to an increase of 0.031 W m -2 radiative forcing, were estimated to be avoided by 2020, which will prevent an additional 0.025 °C increase in temperature. The MP implemented by China has resulted in substantial environmental benefits over the last 30 years. However, owing to the massive use of HFCs as substitutes, the cumulative emissions reached 2286 Mt. CO 2 -eq during 1990-2020, and it will be challenging to phase down HFCs in the environment after China ratified the Kigali Amendment in 2021., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Using the source identification and classification methodology described in UNEP standardized toolkit for dioxin releases, combined with research data over the past decade, the production and release of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) from 6 major sectors in China were inventoried from 2003 to 2020, and were projected until 2025 based on current control measures and relevant industrial plans. The results showed that after ratification of the Stockholm Convention, China's production and release of PCDD/Fs began to decline after peaking in 2007, demonstrating the effectiveness of preliminary control measures. However, the continual expansion of manufacturing and energy sectors, along with the lack of compatible production control technology, reversed the declining trend of production after 2015. Meanwhile, the environmental release continued to decrease, but at a slower rate after 2015. If subject to current policies, production and release would remain elevated with an expanding gap in between. This study also established the congener inventories, revealing the significance of OCDF and OCDD in terms of both production and release, and that of PeCDF and TCDF in terms of environmental impacts. Lastly, through comparison with other developed countries and regions, it was concluded that room for further reduction exists, but can only be achieved through strengthened regulations and improved control measures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Boron primarily exists in the form of agglomerates in ramjet combustion chambers. However, the model used to predict the ignition time of boron agglomerates is usually based on the single-particle assumption, resulting in inaccurate predictions. This study aims to develop a numerical model that can accurately describe the ignition of boron agglomerates. The model is based on the ignition model of a single particle boron proposed by the group of Kuo. Thiele modulus and effectiveness factor are introduced to represent the diffusion resistance of reaction gases in the pores of boron agglomerates. The model includes the necessary physical processes to accurately predict the ignition time. The rates of evaporation and heterogeneous reactions involved in the oxide layer removal process are corrected based on the fact that the diffusion rate of (BO) n in the liquid oxide layer equals to its consumption rate at the oxide-air interface. To evaluate the accuracy of the model, the obtained results for ignition time are compared with experimental data, showing reasonable consistency between them. The model is then applied to investigate the ignition characteristics of boron agglomerates. Parameters, such as initial average pore diameter, oxide layer thicknesses, initial particle diameter, O 2 concentration, H 2 O concentration, and environmental pressure, are studied for their effects on the ignition time. In summary, the boron ignition model established in this study is a powerful tool to investigate the ignition mechanisms and characteristics of boron agglomerates. It can be further coupled with flow analysis for the detailed simulation of turbulent combustion in ramjet combustors., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

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% (CH 2 Cl 2 ) to 81% (CF 3 Cl, 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 CO 2 -equivalent (CO 2 -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, SF 6 accounted for the highest proportion of CO 2 -equiv emissions (24%), followed by HFC-23 (22%), HFC-125 (17%), HFC-134a (13%), NF 3 (10%), CF 4 (5.9%), HFC-143a (3.9%), HFC-32 (3.4%), and HFC-152a (0.2%).

This study aimed to investigate the transmission and molecular epidemiological characteristics of the rmtB gene in Escherichia coli (E. coli) strains isolated from duck farms in Guangdong Province of China from 2018 to 2021. A total of 164 (19.4%, 164/844) rmtB-positive E. coli strains were recovered from feces, viscera, and environment. We performed antibiotic susceptibility tests, pulsed-field gel electrophoresis (PFGE), and conjugation experiments. We obtained the genetic context of 46 rmtB-carrying E. coli isolates and constructed a phylogenetic tree via whole genome sequencing (WGS) and bioinformatic analysis. The isolation rate of rmtB-carrying E. coli isolates in duck farms increased yearly from 2018 to 2020 but decreased in 2021. All rmtB-harboring E. coli strains were multidrug resistant (MDR), and 99.4% of the strains were resistant to more than 10 drugs. Surprisingly, duck- and environment-associated strains similarly showed high MDR. Conjugation experiments revealed that the rmtB gene horizontally cocarried bla CTX-M and bla TEM gene dissemination via IncFII plasmids. Insertion sequences IS26, ISCR1, and ISCR3 were closely associated with the spread of rmtB-harboring E. coli isolates. WGS analysis indicated that ST48 was the most prevalent sequence type. The results of single nucleotide polymorphism (SNP) differences revealed potential clonal transmission between ducks and the environment. Based on One Health principles, we need to strictly use veterinary antibiotics, monitor the distribution of MDR strains, and evaluate the impact of plasmid-mediated rmtB gene on human, animal, and environmental health., Competing Interests: DISCLOSURES The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Global hydrofluorocarbon (HFC) cumulative emissions will be more than 20 Gt CO 2 -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 CO 2 -equiv of cumulative territorial emissions (compared to the 2019 Baseline scenario) during 2020-2060 at an average abatement cost of 9 ± 6 USD/t CO 2 -equiv. Under the near-zero emission (including territorial and abroad) pathway, radiative forcing from HFCs will peak in 2037 (60 ± 6 mW/m 2 ) 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.

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.

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

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., (© 2022. The Author(s).)

Due to their unique breeding pattern, aquatic bird farms are increasingly considered as hotspots in the development and spread of antimicrobial resistance. However, comprehensive studies addressing the whole-genomic features of colistin-resistant bacteria in aquatic bird farms are scarce. Over a 2-year period, we conducted surveillance to determine the whole-genome epidemiology and characterisation of mcr-1-positive Escherichia coli in aquatic bird farms in southeastern coastal China. A total of 100 mcr-1-producing isolates among 654 E. coli strains were recovered from 781 samples collected in 11 aquatic bird farms and 1 veterinary clinic in the Pearl River Delta area. Higher resistance phenotypes to 17 antibiotics were found in mcr-1-positive isolates compared with other isolates. Subsequently, 20 mcr-1-carrying isolates were sequenced to analyse the whole-genomic features. Molecular typing as well as antimicrobial resistance gene and virulence factor profiles of the isolates showed considerable diversity. Three types of genetic backbones of mcr-1 in the isolates were assembled and were identified in diverse broad-host-range plasmids and bacterial species. Pangenome analyses revealed a large genetic pool composed of the isolates. Furthermore, phylogenetic trees both of the isolates in this study and a global data set were built, indicating the spread of the three mcr-1 backbones and the mcr-1-positive isolates among different habitats, farms and even countries. This study highlights that aquatic bird farms may act as an important reservoir for mcr-1-producing E. coli, from which colistin resistance may be spread to diverse habitats, different geographical locations and even across bacterial species., (Copyright © 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

With the successful implementation of the Montreal Protocol on Substances that Deplete the Ozone Layer, the atmospheric abundance of ozone-depleting substances continues to decrease slowly and the Antarctic ozone hole is showing signs of recovery. However, growing emissions of unregulated short-lived anthropogenic chlorocarbons are offsetting some of these gains. Here, we report an increase in emissions from China of the industrially produced chlorocarbon, dichloromethane (CH 2 Cl 2 ). The emissions grew from 231 (213-245) Gg yr -1 in 2011 to 628 (599-658) Gg yr -1 in 2019, with an average annual increase of 13 (12-15) %, primarily from eastern China. The overall increase in CH 2 Cl 2 emissions from China has the same magnitude as the global emission rise of 354 (281-427) Gg yr -1 over the same period. If global CH 2 Cl 2 emissions remain at 2019 levels, they could lead to a delay in Antarctic ozone recovery of around 5 years compared to a scenario with no CH 2 Cl 2 emissions., (© 2021. The Author(s).)

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/cm 2 /h) was significantly higher than that of GL-sol-gel (3.08 ± 0.34 µg/cm 2 /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.

Due to the characteristics of ozone-depleting and high global warming potential, chlorofluorocarbons (CFCs), hydrochlorofluorocarbons (HCFCs) and hydrofluorocarbons (HFCs) have been restricted by the Montreal Protocol and its amendments over the world. Considering that China is one of the main contributors to the emission of halocarbons, a long-term atmospheric observation on major substances including CFC-11 (CCl 3 F), CFC-12 (CCl 2 F 2 ), HCFC-22 (CHClF 2 ), HCFC-141b (CH 3 CCl 2 F), HCFC-142b (CH 3 CClF 2 ) and HFC-134a (CH 2 FCF 3 ) was conducted in five cities (Beijing, Hangzhou, Guangzhou, Lanzhou and Chengdu) of China during 2009-2019. The atmospheric concentrations of CFC-11, CFC-12, HCFC-141b and HCFC-142b all showed declining trends on the whole while those of HCFC-22 and HFC-134a were opposite. A paired sample t-test showed that the ambient mixing ratios of HCFC-22 and HFC-134a in cities were 41.9% and 25.7% higher on average than those in suburban areas, respectively, while the other substances did not show significant regional differences. The annual emissions of halocarbons were calculated using an interspecies correlation method and the results were generally consistent with the published estimates. Discrepancies between bottom-up inventories and the estimates in this study for CFCs emissions were found. Among the most consumed ozone depleting substances (ODSs) in China, CFCs accounted for 75.1% of the ozone depletion potential (ODP)-weighted emissions while HCFCs contributed a larger proportion (58.6%) of CO 2 -equivalent emissions in 2019. China's emissions of HCFC-141b and HCFC-142b contributed the most to the global emission (17.8%-48.0%). The elimination of HCFCs in China will have a crucial impact on the HCFCs phase-out in the world., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: This study aims to compare the performance of an MRI-based composite index (HSI) with conventional MRI-based measures in hippocampal sclerosis (HS) detection and postoperative outcome estimation., Methods: Seventy-two temporal lobe epilepsy (TLE) patients with pathologically confirmed HS and fifteen TLE patients without HS were included retrospectively. The T1-weighted and FLAIR images of these patients were processed with AccuBrain to quantify the hippocampal volume (HV) and the hippocampal FLAIR signal. The HSI index that considered both HV and hippocampal FLAIR signal was also calculated. Two experienced neuropathologists rated the HS severity with the resected tissue and reached an agreement for all cases. The asymmetry indices of the MRI measures were used to lateralize the sclerotic side, and the original MRI measures were applied to detect HS vs. normal hippocampi. Operating characteristic curve (ROC) analyses were performed for these predictions. We also investigated the sensitivity of the ipsilateral MRI measures in characterizing the pathological severity of HS and the associations of the MRI measures with postoperative outcomes (Engel class categories)., Results: With the optimal cutoffs, the asymmetry indices of HSI and HV both achieved excellent performance in differentiating left vs. right HS (accuracy = 100 %), and the absolute value of the asymmetry index of HSI performed best in differentiating unilateral vs. bilateral HS (accuracy = 91.7 %). Regarding the detection of HS, HSI performed better in sensitivity (94.4 % vs. 87.5 %) while HV performed better in specificity (93.6 % vs. 89.4 %) when the contralateral site of unilateral HS and both sides of non-HS patients were considered as the normal reference, and HSI performed even better than HV when only both sides of non-HS patients were considered as the normal reference (AUC: 0.956 vs. 0.934, p = 0.038). The ipsilateral HSI presented the strongest association with the pathological rating of HS severity (r = 0.405, p < 0.001). None of the ipsilateral or contralateral MRI measures was associated with the postoperative outcomes. Among the asymmetry indices, only the absolute value of the asymmetry index of HV presented a significant association with the Engel classifications for the Year 2∼3 visit (r = -0.466, p = 0.004) or the latest visit with >1 year follow-up (r = -0.374, p = 0.003) while controlling for disease duration and follow-up duration., Conclusion: The HSI index and HV presented comparable good performance in HS detection, and HSI may have better sensitivity than HV in differentiating pathological HS severity. Higher magnitude of HV dissymmetry may indicate better post-surgical outcomes for HS patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Nifekalant has been used in the treatment of atrial arrhythmia recently. However, there is no consensus on the preferable nifekalant dose to treat atrial fibrillation (AF). The purpose of this study was to explore efficacy and safety of different doses of nifekalant in the cardioversion of persistent AF. The study was a single-centre, randomized controlled trial. All subjects received nifekalant or placebo intravenously, and the nifekalant was given at the dosage of 0.3, 0.4 or 0.5 mg/kg. Primary efficacy end-point: compared with 0.3 mg group, the rate of cardioversion to sinus rhythm from AF in 0.4 and 0.5 mg group was higher. The 0.4 and 0.5 mg/kg doses were associated with a similar magnitude of efficacy (P > .05). Secondary efficacy end-point: termination rates of AF in the group of 0.4 mg and 0.5 mg were higher than 0.3 mg. Primary safety end-point: the rate of Torsades de Pointes or ventricular fibrillation was numerically lower in the 0.4 mg group than 0.5 mg group (P = .02). Secondary safety end-point: The rates of the majority of other common drug-related adverse events in the group of 0.5 and 0.4 mg were higher than the 0.3 mg group. A 0.4 mg/kg dose of intravenous nifekalant may be recommended during the radiofrequency ablation for persistent AF considering the benefit-risk profile., (© 2020 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

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 (F 0 ) 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 17β-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 F 1 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., (© 2020 John Wiley & Sons, Ltd.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Oxalate and calcium are the major risk factors for calcium oxalate (CaOx) stone formation. However, the exact mechanism remains unclear. This study was designed to confirm the potential function of miR-155-5p in the formation of CaOx induced by oxalate and calcium oxalate monohydrate (COM). The HK-2 cells were treated by the different concentrations of oxalate and COM for 48 h. We found that oxalate and COM treatment significantly increased ROS generation, LDH release, cellular MDA levels, and H 2 O 2 concentration in HK-2 cells. The results of qRT-PCR and western blot showed that expression of NOX2 was upregulated, while that of SOD-2 was downregulated following the treatment with oxalate and COM in HK-2 cells. Moreover, the results of miRNA microarray analysis showed that miR-155-5p was significantly upregulated after oxalate and COM treated in HK-2 cells, but miR-155-5p inhibitor treatment significantly decreased ROS generation, LDH release, cellular MDA levels, and H 2 O 2 concentration in HK-2 cells incubated with oxalate and COM. miR-155-5p negatively regulated the expression level of MGP via directly targeting its 3'-UTR, verified by the Dual-Luciferase Reporter System. In vivo, polarized light optical microphotography showed that CaOx crystal significantly increased in the high-dose oxalate and Ca 2+ groups compared to the control group. Furthermore, IHC analyses showed strong positive staining intensity for the NOX-2 protein in the high-dose oxalate and Ca 2+ -treated mouse kidneys, and miR-155-5p overexpression can further enhance its expression. However, the expression of SOD-2 protein was weakly stained. In conclusion, our study indicates that miR-155-5p promotes oxalate- and COM-induced kidney oxidative stress injury by suppressing MGP expression., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2020 Kehua Jiang et al.)

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., (© 2019 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals, Inc.)

The airborne occurrence, isomer profiles, and phase distribution of perfluoroalkyl acids (PFAAs), including perfluoroalkyl carboxylates (PFCAs) and sulfonates (PFSAs), have received little scientific attention to date. Here we collected gaseous and particulate phase (PM 2.5 ) samples in China, between June and November 2013, using alkalized annular denuders and downstream filters toavoid sampling artefacts associated with traditional air sampling. We analysed the concentrations of 18 linear PFAAs and the branched isomers of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS). Concentrations of total PFAAs were dominated by PFCAs, with a range of 6.6-610 pg/m 3 in the gaseous phase and 2.3-290 pg/m 3 in the particulate phase. Concentrations of total PFCAs were higher in summer than winter in both phases. Branched PFOA isomers accounted for 10-22% of total PFOA in the gaseous phase and 13-24% in the particulate phase, which is close to, but slightly lower than, their abundance in the commercial PFOA mixtures manufactured using the electrochemical fluorination (ECF) process. In contract, branched PFOS isomers accounted for 26-63% of total PFOS in the gaseous phase and 39-77% in the particulate phase, which is much higher than their abundance in commercial PFOS mixtures manufactured by ECF. Most PFCAs had mean particle-associated fractions (Φ) higher than 0.5. PFHxS had a much higher mean Φ (0.65) than linear PFOS (0.31). We hypothesise that PFAAs observed in Beijing air may originate from the local water bodies through processes such as aerosol generation, although transformation of precursors also contribute., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

According to the X-ray crystal structures of CYP17A1 (including its complexes with inhibitors), it is shown that a hydrogen bond exists between CYP17A1 and its inhibitors (such as abiraterone and TOK-001). Previous short MD simulations (50 ns) suggested that the binding of abiraterone to CYP17A1 is stronger than that of TOK-001. In this work, by carrying out long atomistic MD simulations (200 ns) of CYP17A1 and its complexes with abiraterone and TOK-001, we observed a binding mode between CYP17A1 and abiraterone, which is different from the binding mode between CYP17A1 and TOK-001. In the case of abiraterone binding, the unfilled volume in the active site cavity increases the freedom of movement of abiraterone within CYP17A1, leading to the collective motions of the helices G and B' as well as the breaking of hydrogen bond existing between the 3β-OH group of abiraterone and N202 of CYP17A1. However, the unfilled volume in the active site cavity can be occupied by the benzimidazole ring of TOK-001, restraining the motion of TOK-001. By pulling the two inhibitors (abiraterone and TOK-001) out of the binding pocket in CYP17A1, we discovered that abiraterone and TOK-001 were moved from their binding sites to the surface of protein similarly through the channels formed by the helices G and B'. In addition, based on the free energy calculations, one can see that it is energetically favorable for the two inhibitors (abiraterone and TOK-001) to enter into the binding pocket in CYP17A1.

Background The efficacy of nifekalant in preexcited atrial fibrillation ( AF ) has not been assessed. Methods and Results The study populations consisted of patients with sustained preexcited AF (n=51), paroxysmal supraventricular tachycardia (n=201), and persistent AF (n=87). Effects of intravenous infusion of nifekalant were assessed on electrophysiological and clinical parameters. Nifekalant prolonged the shortest preexcited R-R, the average preexcited R-R, and the average R-R intervals from 290±35 to 333±44 ms, 353±49 to 443±64 ms, and 356±53 to 467±75 ms, respectively, in patients with preexcited AF (all P<0.001). Nifekalant also decreased the percentage of preexcited QRS complexes, heart rate, and increased systolic pressure (all P<0.001). Nifekalant terminated AF in 33 of 51 patients (65%). Similar effects were also observed in a subgroup of 12 patients with preexcited AF and impaired left ventricular function. In patients with paroxysmal supraventricular tachycardia, nifekalant significantly prolonged the effective refractory period, the block cycle length of the antegrade accessory pathway, and the atrial effective refractory period (all P<0.001). Nifekalant had no effect on the effective refractory period of the antegrade atrioventricular node. Finally, in patients with persistent AF without an accessory pathway, nifekalant did not significantly decrease the ventricular rate of AF . One patient developed Torsades de Pointes. No other adverse effects were observed. Conclusions Nifekalant prolongs the effective refractory period of the antegrade accessory pathway and atrium without blocking antegrade conduction through the atrioventricular node, leading to slowing and/or to termination of preexcited AF . Thus, nifekalant might be an effective and a relatively safe drug in patients with preexcited AF .

Developing neurons of the peripheral nervous system reach their targets via cues that support directional growth, a process known as axon guidance. In investigating how sympathetic axons reach the heart in mice, we discovered that a combination of guidance cues are employed in sequence to refine axon outgrowth, a process we term second-order guidance. Specifically, endothelin-1 induces sympathetic neurons expressing the receptor Ednra to project to the vena cavae leading to the heart. Endothelin signaling in turn induces expression of the repulsive receptor Plexin-A4, via induction of the transcription factor MEF2C. In the absence of endothelin or plexin signaling, sympathetic neurons misproject to incorrect competing vascular trajectories (the dorsal aorta and intercostal arteries). The same anatomical and physiological consequences occur in Ednra +/- ; Plxna4 +/- double heterozygotes, genetically confirming functional interaction. Second-order axon guidance therefore multiplexes a smaller number of guidance cues in sequential fashion, allowing precise refinement of axon trajectories., Competing Interests: DP, PC, JH, AD, BB, TM No competing interests declared, (© 2019, Poltavski et al.)

Correlation of sex determining region Y-box (SOX)9 and NM23 genes with the incidence and prognosis of prostate cancer (PC) was investigated. SOX9-small interfering ribonucleic acid (siRNA) and NM23-siRNA were constructed and transfected into PC-3 cells. The expression levels of SOX9 and NM23 messenger RNAs (mRNAs) and proteins in PC-3 cells were detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. MTT assay was adopted to examine the proliferation ability of the transfected cells, and Transwell assay was applied to detect the migration ability of the transfected cells. Sixty-three patients with PC and 56 patients with benign prostatic hyperplasia who were treated in Huadu District People's Hospital were enrolled. Correlation analyses were conducted for the relative expression levels of SOX9 and NM23 and the Gleason grade; and the survival curves of the patient SOX9/NM23 (S/N) Cq values were plotted. The proliferation and migration abilities of PC-3 cells were remarkably reduced after low expression of SOX9 (P<0.01), while those of PC-3 cells were significantly improved after low expression of NM23 (P<0.01). Compared with that in tissues of PC patients, the relative expression of SOX9 mRNA in patients with benign prostatic hyperplasia was obviously decreased (P<0.01), while that of NM23 mRNA was significantly elevated (P<0.01). The larger the S/N was, the shorter the patient's survival time would be (P<0.05). The low expression of SOX9 gene can significantly reduce the proliferation and migration abilities of PC cells, which is negatively associated with the incidence and prognosis of patients. The low expression of NM23 gene can markedly enhance the proliferation and migration abilities of PC cells, and it is positively related to the incidence and prognosis of patients.

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.

Dilated cardiomyopathy (DCM) is increasingly indicated as a cause of cardioembolic syndrome, in particular, cardioembolic ischemia stroke. However, the potential risk factors for stroke among DCM patients remain under investigated. DCM patients hospitalized from June 2011 to June 2016 were included. The cases were defined as the group of DCM patients with stroke compared with those without stroke. Clinical characteristic data were collected and compared between the two groups including demographic data, complicated diseases, echocardiography index, and laboratory parameters and estimated glomerular filtration rate (eGFR). A multivariate logistic regression analysis model adjusted by sex and age was used to explore the related risk factors for stroke in DCM patients. A total of 779 hospitalized patients with DCM were included. Of these, 55 (7.1%) had experienced a stroke. Significantly lower eGFR levels (68.03 ± 26.22 vs 79.88 ± 24.25 mL/min/1.73 m 2 , P = .001) and larger left atrial diameters (45.32 ± 7.79 vs 43.25 ± 7.11 mm, P = .04) were found in the group of patients having DCM with stroke compared to those without stroke. When the eGFR was categorized as eGFR >60, 30

The ozone layer depletion and its recovery, as well as the climate influence of ozone-depleting substances (ODSs) and their substitutes that influence climate, are of interest to both the scientific community and the public. Here we report on the emissions of ODSs and their substitute from China, which is currently the largest consumer (and emitter) of these substances. We provide, for the first time, comprehensive information on ODSs and replacement hydrofluorocarbon (HFC) emissions in China starting from 1980 based on reported production and usage. We also assess the impacts (and costs) of controls on ODS consumption and emissions on the ozone layer (in terms of CFC-11-equivalent) and climate (in CO 2 -equivalent). In addition, we show that while China's future ODS emissions are likely to be defined as long as there is full compliance with the Montreal Protocol; its HFC emissions through 2050 are very uncertain. Our findings imply that HFC controls over the next decades that are more stringent than those under the Kigali Amendment to the Montreal Protocol would be beneficial in mitigating global climate change.

Background: Homeodomain (HD) transcription factor (TF) NKX2-1 critical for the regional specification of the medial ganglionic eminence (MGE) as well as promoting the GABAergic and cholinergic neuron fates via the induction of TFs such as LHX6 and LHX8. NKX2-1 defines MGE regional identity in large part through transcriptional repression, while specification and maturation of GABAergic and cholinergic fates is mediated in part by transcriptional activation via TFs such as LHX6 and LHX8. Here we analyze the signaling and TF pathways, downstream of NKX2-1, required for GABAergic and cholinergic neuron fate maturation., Methods: Differential ChIP-seq analysis was used to identify regulatory elements (REs) where chromatin state was sensitive to change in the Nkx2-1cKO MGE at embryonic day (E) 13.5. TF motifs in the REs were identified using RSAT. CRISPR-mediated genome editing was used to generate enhancer knockouts. Differential gene expression in these knockouts was analyzed through RT-qPCR and in situ hybridization. Functional analysis of motifs within hs623 was analyzed via site directed mutagenesis and reporter assays in primary MGE cultures., Results: We identified 4782 activating REs (aREs) and 6391 repressing REs (rREs) in the Nkx2-1 conditional knockout (Nkx2-1cKO) MGE. aREs are associated with basic-Helix-Loop-Helix (bHLH) TFs. Deletion of hs623, an intragenic Tcf12 aRE, caused a reduction of Tcf12 expression in the sub-ventricular zone (SVZ) and mantle zone (MZ) of the MGE. Mutation of LHX, SOX and octamers, within hs623, caused a reduction of hs623 activity in MGE primary cultures., Conclusions: Tcf12 expression in the SVZ of the MGE is mediated through aRE hs623. The activity of hs623 is dependent on LHX6, SOX and octamers. Thus, maintaining the expression of Tcf12 in the SVZ involves on TF pathways parallel and genetically downstream of NKX2-1.

In this paper, a versatile multi-body dynamic algorithm is developed to integrate an incompressible fluid flow with a bio-inspired multibody dynamic system. Of particular interest to the biomimetic application, the algorithm is developed via four properly selected benchmark verifications. The present tool has shown its powerful capability for solving a variety of biomechanics fish swimming problems, including self-propelled multiple degrees of freedom with a rigid undulatory body, multiple deformable fins and an integrated system with both undulatory fish body and flexible fins. The established tool has paved the way for future investigation on more complex bio-inspired robots and live fish, for either propulsion or manoeuvring purposes.

Purpose: The development of acquired resistance to the first-line epidermal growth factor-tyrosine kinase inhibitor (EGFR-TKI) treatment in non-small-cell lung cancer (NSCLC) is inevitable, and most of these patients needed second-line chemotherapy. Furthermore, the optimum chemotherapeutic regimen is unclear. The aim of this meta-analysis was to evaluate the chemotherapeutic regimens "with-pemetrexed" versus "non-pemetrexed" in advanced NSCLC patients who had progressed after first-line EGFR-TKIs., Materials and Methods: We searched PubMed, Embase, Cochrane Library, and the Web of science for relevant clinical trials. Outcomes analyzed were response rate (RR), disease control rate (DCR), 1-year survival rate (1-year SR), progression-free survival (PFS), and overall survival (OS)., Results: One randomized controlled trial (RCT) and three retrospective studies were included in this meta-analysis, covering a total of 354 patients. The results showed that there was no significant difference between with-pemetrexed arm and non-pemetrexed arm in RR (OR 1.43, 95% CI 0.85-2.41, P =0.18), DCR (OR 1.5, 95% CI 0.94-2.39, P =0.09), and 1-year SR (OR 1.47, 95% CI 0.79-2.74, P =0.22). But the with-pemetrexed chemotherapeutic regimens significantly improved the PFS (HR 0.61, 95% CI 0.46-0.81, P =0.0005) and OS (HR 0.62, 95% CI 0.42-0.90, P =0.01)., Conclusion: The second-line with-pemetrexed chemotherapeutic regimens provided significantly longer PFS and OS than non-pemetrexed chemotherapeutic regimens. These findings indicate that the with-pemetrexed chemotherapeutic regimen may be an optimal second-line chemotherapeutic regimen for patients with advanced NSCLC following EGFR-TKI failure., Competing Interests: Disclosure The authors report no conflicts of interest in this work.