MicroRNA-148a-3p suppresses the glycolysis and Cell proliferation by targeting transmembrane protein 54 in liver cancer.

Liver cancer is the fourth most lethal cancer, but the treatment options for liver cancer are usually limited. Metabolic reprogramming is a hallmark of malignancy, ensuring activated cell glycolysis and increased macromolecular precursors required for the proliferation and migration of exuberant cancer cells. MicroRNAs (miRNAs) have been reported to participate in cancer metabolic shifts mainly by directly silencing the expression of specific genes. Here, we identified miR-148a-3p as a negative regulator for glycometabolism and cell proliferation in liver cancer. miR-148a-3p directly targets the 3'UTR of transmembrane protein 54 (TMEM54), leading to the significant inhibition of lactate production, glucose consumption, intracellular ATP level and extracellular acidification rate (ECAR), as well as the repression of the proliferation and colony formation ability of liver cancer cells. miR-148a-3p expression is often down-regulated in liver cancer tissues. In addition, there was a negative correlation between the expression levels of miR-148a-3p and TMEM54 in liver cancer tissues. Moreover, the low miR-148a-3p expression levels or high TMEM54 expression levels were associated with poorer prognosis in hepatocellular carcinoma (HCC) patients. Together, these findings support that the miR-148a-3p/TMEM54 regulatory pathway regulates the glycometabolism and cell proliferation in liver cancer, which is a possible target for the diagnosis and treatment of liver cancer.

Dynamic Traffic Data in Machine-Learning Air Quality Mapping Improves Environmental Justice Assessment.

Air pollution poses a critical public health threat around many megacities but in an uneven manner. Conventional models are limited to depict the highly spatial- and time-varying patterns of ambient pollutant exposures at the community scale for megacities. Here, we developed a machine-learning approach that leverages the dynamic traffic profiles to continuously estimate community-level year-long air pollutant concentrations in Los Angeles, U.S. We found the introduction of real-world dynamic traffic data significantly improved the spatial fidelity of nitrogen dioxide (NO2), maximum daily 8-h average ozone (MDA8 O3), and fine particulate matter (PM2.5) simulations by 47%, 4%, and 15%, respectively. We successfully captured PM2.5 levels exceeding limits due to heavy traffic activities and providing an "out-of-limit map" tool to identify exposure disparities within highly polluted communities. In contrast, the model without real-world dynamic traffic data lacks the ability to capture the traffic-induced exposure disparities and significantly underestimate residents' exposure to PM2.5. The underestimations are more severe for disadvantaged communities such as black and low-income groups, showing the significance of incorporating real-time traffic data in exposure disparity assessment.

Integrated Benefits of Synergistically Reducing Air Pollutants and Carbon Dioxide in China.

China's advancements in addressing air pollution and reducing CO2 emissions offer valuable lessons for collaborative strategies to achieve diverse environmental objectives. Previous studies have assessed the mutual benefits of climate policies and air pollution control measures on one another, lacking an integrated assessment of the benefits of synergistic control attributed to refined measures. Here, we comprehensively used coupled emission inventory and response models to evaluate the integrated benefits and synergy degrees of various measures in reducing air pollutants and CO2 in China during 2013-2021. Results indicated that the implemented measures yielded integrated benefits value at 6.7 (2.4-12.6) trillion Chinese Yuan. The top five contributors, accounting for 55%, included promoting non-thermal power, implementing end-of-pipe control technologies in power plants and iron and steel industry, replacing residential scattered coal, and saving building energy. Measures demonstrating high synergies and integrated benefits per unit of reduction (e.g., green traffic promotion) yielded low benefits mainly due to their low application, which are expected to gain greater implementation and prioritization in the future. Our findings provide insights into the effectiveness and limitations of strategies aimed at joint control. By ranking these measures based on their benefits and synergy, we offer valuable guidance for policy development in China and other nations with similar needs.

From COVID-19 to future electrification: Assessing traffic impacts on air quality by a machine-learning model.

The large fluctuations in traffic during the COVID-19 pandemic provide an unparalleled opportunity to assess vehicle emission control efficacy. Here we develop a random-forest regression model, based on the large volume of real-time observational data during COVID-19, to predict surface-level NO2, O3, and fine particle concentration in the Los Angeles megacity. Our model exhibits high fidelity in reproducing pollutant concentrations in the Los Angeles Basin and identifies major factors controlling each species. During the strictest lockdown period, traffic reduction led to decreases in NO2 and particulate matter with aerodynamic diameters <2.5 µm by -30.1% and -17.5%, respectively, but a 5.7% increase in O3 Heavy-duty truck emissions contribute primarily to these variations. Future traffic-emission controls are estimated to impose similar effects as observed during the COVID-19 lockdown, but with smaller magnitude. Vehicular electrification will achieve further alleviation of NO2 levels.

Updating On-Road Vehicle Emissions for China: Spatial Patterns, Temporal Trends, and Mitigation Drivers.

Vehicle emissions in China have been decoupled from rapid motorization owing to comprehensive control strategies. China's increasingly ambitious goals for better air quality are calling for deep emission mitigation, posing a need to develop an up-to-date emission inventory that can reflect the fast-developing policies on vehicle emission control. Herein, large-sample vehicle emission measurements were collected to update the vehicle emission inventory. For instance, ambient temperature correction modules were developed to depict the remarkable regional and seasonal emission variations, showing that the monthly emission disparities for total hydrocarbon (THC) and nitrogen oxide (NOX) in January and July could be up to 1.7 times in northern China. Thus, the emission ratios of THC and NOX can vary dramatically among various seasons and provinces, which have not been considered well by previous simulations regarding the nonlinear atmospheric chemistry of ozone (O3) and fine particulate matter (PM2.5) formation. The new emission results indicate that vehicular carbon monoxide (CO), THC, and PM2.5 emissions decreased by 69, 51, and 61%, respectively, during 2010-2019. However, the controls of NOX and ammonia (NH3) emissions were not as efficient as other pollutants. Under the most likely future scenario (PC [1]), CO, THC, NOX, PM2.5, and NH3 emissions were anticipated to reduce by 35, 36, 35, 45, and 4%, respectively, from 2019 to 2025. These reductions will be expedited with expected decreases of 56, 58, 74, 53, and 51% from 2025 to 2035, which are substantially promoted by the massive deployment of new energy vehicles and more stringent emission standards. The updated vehicle emission inventory can serve as an important tool to develop season- and location-specific mitigation strategies of vehicular emission precursors to alleviate haze and O3 problems.

Emission Measurements on a Large Sample of Heavy-Duty Diesel Trucks in China by Using Mobile Plume Chasing.

Real-world heavy-duty diesel trucks (HDTs) were found to emit far more excess nitrogen oxides (NOX) and black carbon (BC) pollutants than regulation limits. It is essential to systematically evaluate on-road NOX and BC emission levels for mitigating HDT emissions. This study launched 2109 plume chasing campaigns for NOX and BC emissions of HDTs across several regions in China from 2017 to 2020. It was found that NOX emissions had limited reductions from China III to China V, while BC emissions of HDTs exhibited high reductions with stricter emission standard implementation. This paper showed that previous studies underestimated 18% of NOX emissions in China in 2019 and nearly half of the real-world NOX emissions from HDTs (determined by updating the emission trends of HDTs) exceeded the regulation limits. Furthermore, the ambient temperature was identified as a primary driver of NOX emissions for HDTs, and the low-temperature penalty has caused a 9-29% increase in NOX emissions in winter in major regions of China. These results would provide important data support for the precise control of the NOX and BC emissions from HDTs.

Carbon Sequestration Potential of Biomass Production along Highways in China.

In response to climate change, China is making great efforts to increase the green area for carbon sequestration. Road verges, as marginal land with favorable conditions for plant growth and ease of transportation, can be used for biomass production, but the biomass production and carbon sequestration potential have not been assessed. Here, we mapped the biomass production potential of road verges in China by combining a biomass model and Geographic Information System and then evaluated the effect of road runoff and CO2 fertilization on the production according to the runoff coefficient and vehicle emission inventory. Nationwide, road verges can produce 15.86 Mt C yr-1 of biomass. Road runoff contributes to a biomass production of 1.26 Mt C yr-1 through increasing soil water availability, which mainly occurs in arid regions. The CO2 fertilization effect by vehicle emission is considerable in Eastern and Southern China, contributing to a production of 0.09 Mt C yr-1. Life cycle assessment shows that major road verges in China have a carbon sequestration potential of 6.87 Mt C yr-1 currently. Our results revealed that road verges can make a significant contribution to carbon neutrality under proper management.

Vehicular Ammonia Emissions Significantly Contribute to Urban PM2.5 Pollution in Two Chinese Megacities.

Ammonia (NH3) plays a vital role in the formation of fine particulate matter (PM2.5). Prior studies have primarily focused on the control of agricultural NH3 emissions, the dominant source of anthropogenic NH3 emissions. The air quality impact from vehicular NH3 emissions, which could be particularly important in urban areas, has not been adequately evaluated. We developed high-resolution vehicular NH3 emission inventories for Beijing and Shanghai based on detailed link-level traffic profiles and conducted atmospheric simulations of ambient PM2.5 concentrations contributed by vehicular NH3 emissions. We found that vehicular NH3 emissions shared high proportions among total anthropogenic NH3 emissions in the urban areas of Beijing (86%) and Shanghai (45%), where vehicular NH3 was primarily emitted by gasoline vehicles. Local vehicular NH3 emissions could be responsible for approximately 3% of urban PM2.5 concentrations during wintertime, and the contributions could be much higher during polluted periods (∼3 µg m-3). We also showed that controlling vehicular NH3 emissions will be effective and feasible to alleviate urban PM2.5 pollution for megacities in the near future.

Lateral sinus floor elevation in patients with sinus floor defects: A retrospective study with a 1- to 9-year follow-up.

OBJECTIVES: We aimed to retrospectively evaluate the long-term clinical outcomes of lateral sinus floor elevation (LSFE) in patients with sinus floor defects. MATERIALS AND METHODS: Between 2008 and 2020, patients with sinus floor defects were recruited after confirmation on preoperative cone-beam computed tomography (CBCT). The split-thickness flap technique with a palatal crestal incision was used to manage tissue adhesion in the bone defects area. A resorbable collagen membrane was used to close the sinus floor defects from the crestal side before bone substitute placement. Of 58 implants, 47 (81.0%) were placed after an 8-month healing period, whereas 11 were placed simultaneously. Patients were followed up by radiography and clinical examination for 1-9 years. Finally, the cumulative survival rate (CSR) of implants, surgical complications, and marginal bone loss (MBL) were recorded and analyzed. RESULTS: In total, LSFE was performed in 36 sinuses (35 patients) with sinus floor defects, of which surgery was completed in 35 sinuses (97.2%) in the first attempt. Schneiderian membrane perforations (SMP) occurred in 10/36 (27.8%) sinuses; nine were repaired carefully, whereas one surgery was suspended due to complicated SMP, and successful re-entry LSFE was performed 4 months later. After a follow-up period of 1-9 years, the CSR was 96.5% at the 1-year, 3-year, 5-year, and 7-year follow-ups and 64.3% at the 8-year follow-up. CONCLUSION: Within the limitations of this study, sinus floor defects seem not to compromise LSFE therapy after appropriate management and long-term clinical outcomes are predictable.

Copy number variations of LRRFIP1 gene and the relationship with growth traits in four Chinese sheep.

CNVs (copy number variations) are the novel and common structural variants that could cover entire genes found in plenty of species. CNV may influence economically important traits or disease susceptibility in livestock species. Based on the whole genome resequencing results, we found that there was a CNV region on the LRRFIP1 gene. Then we used qPCR to detect the copy number type distribution in 553 individuals of four sheep breeds and used them for association analysis. The results showed that: (1) In the CKS, the sheep with gain type had a larger heart girth (p = 0.049). (2) For the HS, the CNV could significantly affect rump breadth (p = 0.037) and circumference of the cannon (p = 0.035). And the sheep with median type showed better performance in rump breadth and circumference of cannon. (3) At the STHS, the CNV was significantly correlated with chest width (p = 0.000) with loss type as the most favorable CNV type. Meanwhile, the best was the loss type, and the lowest was the median. (4) This CNV had no significant effect on the LTHS. So, the CNV of LRRFIP1 was related to the growth traits of these three sheep breeds and it may be used as a molecular marker for sheep.

Cinnamaldehyde Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating TLR4/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation.

Ulcerative colitis (UC) is a chronic inflammatory gastrointestinal disease mainly associated with immune dysfunction and microbiota disturbance. Cinnamaldehyde (CIN) is an active ingredient of Cinnamomum cassia with immunomodulatory and anti-inflammatory properties. However, the therapeutic effect and detailed mechanism of CIN on UC remains unclear, and warrant further dissection. In this study, network pharmacology and molecular docking analyses were introduced to predict the potential targets and mechanism of CIN against UC. The therapeutic effect and the predicted targets of CIN on UC were further validated by in vivo and in vitro experiments. Seven intersection targets shared by CIN and UC were obtained, and four hub targets, i. e., toll-like receptor 4 (TLR4), transcription factor p65 (NF-κB), NF-kappa-B inhibitor alpha (IκBα), prostaglandin G/H synthase 2 (COX2) were acquired, which were mainly involved in NF-κB, tumor necrosis factor (TNF), Toll-like receptor and NOD-like receptor signaling pathways. CIN alleviated the symptoms of dextran sulfate sodium (DSS)-induced colitis by decreasing the disease active index (DAI), restoring colon length, and relieving colonic pathology. CIN attenuated systemic inflammation by reducing serum myeloperoxidase (MPO), TNF-α, interleukin-6 (IL-6), and interleukin-1ß (IL-1ß), down-regulating TLR4, phosphorylated-NF-κB (p-NF-κB), phosphorylated-IκBα (p-IκBα), and COX2 expression in colonic tissues, and decreasing NOD-like receptor protein 3 (NLRP3), Caspase-1, and IL-1ß protein expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. These results indicate that CIN alleviates DSS-induced colitis inflammation by modulating TLR4/NF-κB signaling pathway and NLRP3 inflammasome activation.

A molecular marker of milk composition traits in NCAM2 gene of Chinese Holstein.

The aim of this study was to detect the novel copy number variation (CNV) locus of NCAM2 gene in Chinese Holstein, and to analyze the effect of the novel CNV locus in NCAM2 gene on milk composition traits. The novel CNV locus of NCAM2 gene in 310 Chinese Holstein was detected by real-time quantitative fluorescent PCR (qPCR) and association analysis was performed between the novel CNV locus in NCAM2 gene and milk composition traits in Chinese Holstein. There are three CNV types of NCAM2 gene in Chinese Holstein: gain (increased copy number), median (normal copy number) and loss (deleted copy number). Statistical analysis revealed that there was a significant association between CNV types and milk fat rate (p < 0.05). Moreover, we also discovered that the milk production and milk protein rate of gain type is higher than that of loss type, but that of mediate type is lower than that of loss type. However, in terms of somatic cell score, loss type is higher than that of gain type, but that of mediate type is lower than that of gain type. These observations suggested that gain type can be used as a candidate molecular genetic marker of milk fat rate.HighlightsThe CNVs of the NCAM2 gene were detected and validated in Chinese Holstein.The type of CNV was successfully implemented using qPCR.The statistical analysis indicated that the CNV of the NCAM2 gene are significantly associated with milk fat rate.

Copy number variation of the USP16 gene and its association with milk traits in Chinese Holstein cattle.

Copy number variations (CNVs) were similar to single nucleotide polymorphisms (SNPs) and insertion-deletion (InDel), regarded as genetic variations in many species. CNV is defined as the variable change of DNA segment length compared with the reference genome, including gains or losses from 50 bp to several mega bases. The functions of USP16 gene are diverse, such as regulating the cell cycle, DNA damage, histone H2A deubiquitination or mitotic nuclear division. To analyze the relationship between CNV of USP16 gene and milk traits in Chinese Holstein, we used qPCR to detect the individuals of Chinese Holstein (n = 180). The results showed that the effect of USP16 gene CNV on daily milk yield and fat percentage had significant difference (p < 0.05). The gain was the advantage type in daily milk yield and the loss was the advantage type in fat percentage. Therefore, CNV of USP16 gene is an important factor of milk traits in Chinese Holstein. Meanwhile, it may be used as a molecular marker for assisted selection of milk traits in Chinese Holstein, which provides a theoretical basis for the genetic improvement of cow breeds in China.

DNA methylation status of SERPINA3 gene involved in mRNA expression in three cattle breeds.

DNA methylation could take part in the gene expression and acts an important role in muscle development. In this study, DNA methylation and expression in adipose and muscle tissues were examined at the same time to evaluate the extent of epigenetic modifications and gene expression on the differentially methylated region (DMR) in SERPINA3. Chain reaction of bisulfite sequencing polymerase (BSP) was used to compared difference among DNA methylation patterns. The result of quantitative real-time PCR (qPCR) analysis showed that there was an extensive expression of SERPINA3 gene in tissue and there was a significant difference existing in muscle and adipose between Jiaxian cattle and individual of other breeds with increasing hybridization (p < 0.05). The statistic analyses indicated that DNA methylation patterns had a significant influence to the level of mRNA in tissue of fat and muscle. This study may be an important reference for investigating development of muscle tissue in cattle, and may promote the process of cattle molecular breeding.

Transcriptome-wide study revealed m6A regulation of embryonic muscle development in Dingan goose (Anser cygnoides orientalis).

BACKGROUND: The number of myofiber is determined during the embryonic stage and does not increase during the postnatal period for birds, including goose. Thus, muscle production of adult goose is pre-determined during embryogenesis. Previous studies show N6-methyladenosine (m6A) is an important regulator for skeletal muscle development of birds and miRNAs play as a co-regulator for the skeletal muscle development in birds. Herein, we sequenced m6A and miRNA transcriptomes to investigate the profiles of m6A and their potential mechanism of regulating breast muscle development in Dingan Goose. RESULTS: We selected embryonic 21th day (E21) and embryonic 30th day (E30) to investigate the roles of transcriptome-wide m6A modification combining with mRNAs and miRNAs in goose breast muscle development. In this study, m6A peaks were mainly enriched in coding sequence (CDS) and start codon and397 genes were identified as differentially methylated genes (DMGs). GO and KEGG analysis showed that DMGs were highly related to cellular and metabolic process and that most DMGs were enriched in muscle-related pathways including Wnt signaling pathway, mTOR signaling and FoxO signaling pathway. Interestingly, a negative correlation between m6A methylation level and mRNA abundance was found through the analysis of m6A-RNA and RNA-seq data. Besides, we found 26 muscle-related genes in 397 DMGs. We also detected 228 differentially expressed miRNAs (DEMs), and further found 329 genes shared by the target genes of DEMs and DMGs (m6A-miRNA-genes), suggesting a tightly relationship between DEMs and DMGs. Among the m6A-miRNA-genes, we found 10 genes are related to breast muscle development. We further picked out an m6A-miRNA-gene, PDK3, from the 10 genes to visualize it and the result showed differentially methylated peaks on the mRNA transcript consistent with our m6A-seq results. CONCLUSION: GO and KEGG of DMGs between E21 and E30 showed most DMGs were muscle-related. In total, 228 DEMs were found, and the majority of DMGs were overlapped with the targets of DEGs. The differentially methylated peaks along with an m6A-miRNA-gene, PDK3, showed the similar results with m6A-seq results. Taken together, the results presented here provide a reference for further investigation of embryonic skeletal muscle development mechanism in goose.

Copy number variation of MYLK4 gene and its growth traits of Capra hircus (goat).

Copy number variation (CNV) is a form of genetic variation caused by genome rearrangement, with abnormal fragments ranging from 50 bp to Mb. And, CNV is closely related to disease, growth and reproductive shape of livestock. As a member of myosin light chain kinase (MYLK) family with serine/threonine specificity, MYLK4 belongs to an enzyme encoded by MYLK4 gene. Although MYLK4 is a recognized kinase, its function has yet to be revealed in subsequent studies. This study aims to analyze CNV and genetic effects of MYLK4 gene in goats. We used qPCR to detect CNV of MYLK4 gene in African Nubian goat (n = 32), Guizhou black goat (n = 196) and Guizhou white goat (n = 95), respectively, and correlated CNV data of MYLK4 gene with goat growth traits in Chinese goats. The results showed that the effect of MYLK4 gene CNV on body weight, body length and body height of goats had significantly different (p < 0.05, Q < 0.05), in which CNV showed better growth traits in type of deletion. Therefore, CNV of MYLK4 gene can be used as a molecular marker for assisted selection of goat growth traits, which provides a theoretical basis for the genetic improvement of goat breeds in China.

Determination of genetic effects of SERPINA3 on important growth traits in beef cattle.

Serine protease inhibitor protein 3 (serpin peptidase inhibitor, clade A, member 3, SERPINA3) is a member of the serpin superfamily, probably related to the yield and quality of muscle. This study focuses on the relationship between SERPINA3 gene polymorphism and growth traits in beef cattle. The study first uses sequencing pooled DNA samples (Pool-Seq), PCR-RFLP and Tetra-primer ARMS-PCR techniques to determine the genetic polymorphisms of SERPINA3 in 765 beef cattle. Then, the polymorphic loci were correlated with the growth characters of cattle. Five SNPs (SNP1:A-648G, SNP2:T6496A, SNP3:G2495A, SNP4:T2595A, SNP5:A2615G) were found, located in the promoter, introns 5 and SNP 3, 4, 5 were in exons 2, respectively. The observed He was from 0.44 to 0.5, Ne were approaching 2 (1.78 to 2.00). The maximum and minimum PIC (polymorphism information content) values were 0.37 and 0.34, respectively. The association analysis results showed that the SNPs had a significant height in the chest girth and body length. (p < 0.05 or p < 0.01). This will provide important information for the rapid breeding of Chinese yellow cattle and the establishment of a molecular genetic marker database.

Exploring genotype-phenotype relationships of the CRABP2 gene on growth traits in beef cattle.

Cellular retinoic acid binding protein 2 (CRABP2) is essential to myoblast differentiation. However, there was no report about the function of CRABP2 gene in cattle. This study explored the association of CRABP2 gene polymorphisms with growth traits in cattle breeds by several methods, such as DNA sequencing, PCR, PCR-RFLP and forced PCR-RFLP. Two sequence variants were determined. There were 621 individuals in six cattle breeds from China for the experiment, and three breeds were used to test validation of polymorphisms and extent of linkage disequilibrium (LD). The results showed that both SNPs (SNP1, g.2458 G > T, SNP2, g.3878 G > A) were in intron1. Two SNPs were in low linkage disequilibrium. Association analysis suggested that SNP1 had the significant difference on growth traits with body height, height at hip cross and body slanting length (P < .05), while SNP2 showed a significant difference in growth traits with body height, height at hip cross and body slanting length(P < .05). The results of this investigation displayed that the CRABP2 gene is an available candidate gene and may be used for breed selection and conservation.

Genetic Variant of MYLK4 Gene and its Association with Growth Traits in Chinese Cattle.

As a member of MYLK family, MYLK4 gene may play a vital role in muscle development. In this study, one novel single-nucleotide polymorphism (SNP) was identified the bovine MYLK4 by sequencing pooled DNA samples (pool-Seq) and forced polymerase chain reaction-restriction fragment length polymorphism (forced PCR-RFLP) methods. Overall, we reported one mutation (SNP1) in the intron 10 region within the bovine MYLK4 gene in 559 individuals representing five main cattle breeds from China (Nanyang, NY; Qinchuan; Jiaxian, JX; Pinan cattle; and Caidamu cattle, CDM). Genotype AA and allele A were predominant in the QC, PN, and XN populations. Association analysis with growth traits in the QC breed showed that the animals with genotype GG had significantly greater chest breadth and hip width (P < 0.05). Meanwhile, the genotype GG was strongly associated with withers height and body length than those with genotype AA (P < 0.01 or P < 0.05) at 12 months in the NY breed. These statistical results exhibited that the MYLK4 gene might be a potential candidate gene to improve cattle's growth traits, and the SNP could be used as molecular markers in early marker-assisted selection (MAS) in beef cattle breeding program.