Structural basis for human Cav3.2 inhibition by selective antagonists.

The Cav3.2 subtype of T-type calcium channels has been targeted for developing analgesics and anti-epileptics for its role in pain and epilepsy. Here we present the cryo-EM structures of Cav3.2 alone and in complex with four T-type calcium channel selective antagonists with overall resolutions ranging from 2.8 Å to 3.2 Å. The four compounds display two binding poses. ACT-709478 and TTA-A2 both place their cyclopropylphenyl-containing ends in the central cavity to directly obstruct ion flow, meanwhile extending their polar tails into the IV-I fenestration. TTA-P2 and ML218 project their 3,5-dichlorobenzamide groups into the II-III fenestration and place their hydrophobic tails in the cavity to impede ion permeation. The fenestration-penetrating mode immediately affords an explanation for the state-dependent activities of these antagonists. Structure-guided mutational analysis identifies several key residues that determine the T-type preference of these drugs. The structures also suggest the role of an endogenous lipid in stabilizing drug binding in the central cavity.

Quantum Light Generation Based on GaN Microring toward Fully On-Chip Source.

An integrated quantum light source is increasingly desirable in large-scale quantum information processing. Despite recent remarkable advances, a new material platform is constantly being explored for the fully on-chip integration of quantum light generation, active and passive manipulation, and detection. Here, for the first time, we demonstrate a gallium nitride (GaN) microring based quantum light generation in the telecom C-band, which has potential toward the monolithic integration of quantum light source. In our demonstration, the GaN microring has a free spectral range of 330 GHz and a near-zero anomalous dispersion region of over 100 nm. The generation of energy-time entangled photon pair is demonstrated with a typical raw two-photon interference visibility of 95.5±6.5%, which is further configured to generate a heralded single photon with a typical heralded second-order autocorrelation g_{H}^{(2)}(0) of 0.045±0.001. Our results pave the way for developing a chip-scale quantum photonic circuit.

Single-Shot Laser-Induced Switching of an Exchange Biased Antiferromagnet.

Ultrafast manipulation of magnetic order has challenged the understanding of the fundamental and dynamic properties of magnetic materials. So far single-shot magnetic switching has been limited to ferrimagnetic alloys, multilayers, and designed ferromagnetic (FM) heterostructures. In FM/antiferromagnetic (AFM) bilayers, exchange bias (He ) arises from the interfacial exchange coupling between the two layers and reflects the microscopic orientation of the antiferromagnet. Here the possibility of single-shot switching of the antiferromagnet (change of the sign and amplitude of He ) with a single femtosecond laser pulse in IrMn/CoGd bilayers is demonstrated. The manipulation is demonstrated in a wide range of fluences for different layer thicknesses and compositions. Atomistic simulations predict ultrafast switching and recovery of the AFM magnetization on a timescale of 2 ps. The results provide the fastest and the most energy-efficient method to set the exchange bias and pave the way to potential applications for ultrafast spintronic devices.

CGA alleviates LPS-induced inflammation and milk fat reduction in BMECs through the NF-κB signaling pathway.

Mastitis is an easy clinical disease in dairy cows, which seriously affects the milk yield and quality of dairy cows. Chlorogenic acid (CGA), a polyphenolic substance, is abundant in Eucommia ulmoides leaves and has anti-inflammatory and anti-oxidative stress effects. Here, we explore whether CGA attenuated lipopolysaccharide (LPS)-induced inflammation and decreased milk fat in bovine mammary epithelial cells (BMECs). 10 µg/mL LPS was used to induce mastitis in BMECs. QRT-PCR, Western blotting, oil red O staining, and triglyceride (TG) assay were used to examine the effects of CGA on BMECs, including inflammatory response, oxidative stress response, and milk fat synthesis. The results showed that CGA repaired LPS-induced inflammation in BMECs. The expression of IL-6, IL-8, TNF-α, IL-1ß, and iNOS was decreased, and the expression levels of CHOP, XCT, NRF2, and HO-1 were increased, which reduced the oxidative stress level of cells and alleviated the reduction of milk fat synthesis. In addition, the regulation of P65 phosphorylation by CGA suggests that CGA may exert its anti-inflammatory and anti-oxidative effects through the NF-κB signaling pathway. Our study showed that CGA attenuated LPS-induced inflammation and oxidative stress, and restored the decrease in milk fat content in BMECs by regulating the NF-κB signaling pathway.

Effects of dissolved organic matter, pH and nutrient on ciprofloxacin bioaccumulation and toxicity in duckweed.

Water pollution induced by antibiotics has garnered considerable concern, necessitating urgent and effective removal methods. This study focused on exploring ciprofloxacin (CIP) removal by duckweed and assessing CIP bioaccumulation and toxic effects within duckweed under varying dissolved organic matter categories, pH levels, and nutrient (nitrogen (N) and phosphorus (P)) levels. The results revealed the proficient and rapid elimination of CIP from water by duckweed, resulting in 86.17 % to 92.82 % removal efficiency at the end of the 7-day experiment. Across all exposure groups, varying degrees of CIP bioaccumulation in duckweed were evident, with uptake established as a primary pathway for CIP elimination within this plant. Additionally, five CIP metabolites were identified in duckweed tissues. Interestingly, the presence of humic acid (HA) and fulvic acid (FA) reduced CIP absorption by duckweed, with FA yielding a more pronounced impact. Optimal CIP removal was recorded at a pH of 7.5, while duckweed displayed heightened physiological stress induced by CIP at pH 8.5. Although the influence of N and P concentrations on CIP removal by duckweed was modest, excessive N and P levels intensified the physiological strain of CIP on duckweed.

Berbamine targets cancer stem cells and reverses cabazitaxel resistance via inhibiting IGF2BP1 and p-STAT3 in prostate cancer.

BACKGROUND: Cancer stem cells (CSCs) are a small subpopulation of tumor cells with the capability of self-renewal and drug resistance, leading to tumor progression and disease relapse. Our study aimed to investigate the antitumor effect of berbamine, extracted from berberis amurensis, on prostate CSCs. METHODS: Sphere formation was used to collect prostate CSCs. The viability, proliferation, invasion, migration, and apoptosis assays were used to evaluate the antitumor effect of berbamine on prostate CSCs. Prostate CSC markers were analyzed by flow cytometry and qRT-PCR. Small RNA sequencing analysis was conducted to analyse miRNAs. Exosomes were extracted using the ExoQuick-TC kit and verified by testing exosomal markers using western blot. RESULTS: Berbamine targets prostate CSCs. Additionally, berbamine enhanced the antitumor effect of cabazitaxel, a second-line chemotherapeutic drug for advanced prostate cancer, and re-sensitized Cabazitaxel-resistant PCa cells (CabaR-DU145) to cabazitaxel by inhibiting ABCG2, CXCR4, IGF2BP1, and p-STAT3. Berbamine enhanced the expression of let-7 miRNA family and miR-26b and influenced the downstream targets IGF2BP1 and p-STAT3, respectively. Silencing CXCR4 and ABCG2 downregulated the expression of IGF2BP1 and p-STAT3, respectively. Importantly, berbamine enhanced also levels of exosomal let-7 family and miR-26b, suggesting that berbamine possibly influences the expression of let-7 family and miR-26b through exosome delivery. Exosomes derived from berbamine-treated CabaR-DU145 cells re-sensitized the cells to cabazitaxel. CONCLUSION: Berbamine enhanced the toxic activity of cabazitaxel and reversed cabazitaxel resistance potentially through CXCR4/exosomal let-7/IGF2BP1 and ABCG2/exosomal miR-26b/p-STAT3 axes.

MSI2 Modulates Unsaturated Fatty Acid Metabolism by Binding FASN in Bovine Mammary Epithelial Cells.

The regulation of fatty acid metabolism is crucial for milk flavor and quality. Therefore, it is important to explore the genes that play a role in fatty acid metabolism and their mechanisms of action. The RNA-binding protein Musashi2 (MSI2) is involved in the regulation of numerous biological processes and plays a regulatory role in post-transcriptional translation. However, its role in the mammary glands of dairy cows has not been reported. The present study examined MSI2 expression in mammary glands from lactating and dry milk cows. Experimental results in bovine mammary epithelial cells (BMECs) showed that MSI2 was negatively correlated with the ability to synthesize milk fat and that MSI2 decreased the content of unsaturated fatty acids (UFAs) in BMECs. Silencing of Msi2 increased triglyceride accumulation in BMECs and increased the proportion of UFAs. MSI2 affects TAG synthesis and milk fat synthesis by regulating fatty acid synthase (FASN). In addition, RNA immunoprecipitation experiments in BMECs demonstrated for the first time that MSI2 can bind to the 3'-UTR of FASN mRNA to exert a regulatory effect. In conclusion, MSI2 affects milk fat synthesis and fatty acid metabolism by regulating the triglyceride synthesis and UFA content through binding FASN.

Occurrence, Bioaccumulation, Metabolism and Ecotoxicity of Fluoroquinolones in the Aquatic Environment: A Review.

In recent years, there has been growing concern about antibiotic contamination in water bodies, particularly the widespread presence of fluoroquinolones (FQs), which pose a serious threat to ecosystems due to their extensive use and the phenomenon of "pseudo-persistence". This article provides a comprehensive review of the literature on FQs in water bodies, summarizing and analyzing contamination levels of FQs in global surface water over the past three years, as well as the bioaccumulation and metabolism patterns of FQs in aquatic organisms, their ecological toxicity, and the influencing factors. The results show that FQs contamination is widespread in surface water across the surveyed 32 countries, with ciprofloxacin and norfloxacin being the most heavy contaminants. Furthermore, contamination levels are generally higher in developing and developed countries. It has been observed that compound types, species, and environmental factors influence the bioaccumulation, metabolism, and toxicity of FQs in aquatic organisms. FQs tend to accumulate more in organisms with higher lipid content, and toxicity experiments have shown that FQs exhibit the highest toxicity to bacteria and the weakest toxicity to mollusk. This article summarizes and analyzes the current research status and shortcomings of FQs, providing guidance and theoretical support for future research directions.

The development of a clinical research educational training for community health workers using the joint task force for clinical trial competency framework.

Introduction: The NYU Clinical & Translational Science Institute, in collaboration with a number of community-engaged initiatives, developed a training for community health workers (CHWs) to enhance health literacy about clinical research. This innovative research training provides CHWs with a basic level of competency in clinical research to convey the importance of research to communities and better advocate for their health needs. CHWs are an underutilized resource to engage diverse populations in clinical research. The training also addresses the need to expand and diversify the clinical research workforce-integrating CHWs into research teams and connecting underserved populations with research opportunities to enhance quality of care. Methods: Structured individual interviews and focus group sessions were held with CHWs as well as clinical research faculty and staff to identify knowledge gaps in clinical research and identify best practices for educating community members on research. Using the Joint Task Force (JTF) for Clinical Trial Competency framework, an online course was developed consisting of 28 modules offered asynchronously for internal and external audiences. Topics include the fundamentals of clinical research, scientific concepts and research design, research ethics, study management, clinical study operations, communications, and teamwork, as well as the importance of diversity and equity in research and the barriers to participation. Results: Learning was evaluated using multiple choice questions after each module to ensure the fundamental level of knowledge was obtained. A separate survey, completed at the conclusion of the course, evaluated the quality of training. Discussion: The course aims to enhance the knowledge and skills of CHWs to help promote greater understanding of clinical research within the communities they serve, including the risks and benefits of clinical research and opportunities for participation. As members of the research team, community stakeholders can help design interventions tailored to the unique needs, culture, and context of their communities. In addition, this research training equips trainees with skills to engage the community actively, involving them in the research process and ensuring community priorities are represented in research through more community engaged processes.

Corrigendum: The disease associated Tau35 fragment has an increased propensity to aggregate compared to full-length tau.

[This corrects the article DOI: 10.3389/fmolb.2021.779240.].

Preparation of chitosan/citral forward osmosis membrane via Schiff base reaction with enhanced anti-bacterial properties.

In this study, hydrogels generated by the Schiff base reaction between citral and chitosan (CS) were used for the first time to improve the anti-bacterial property of forward osmosis (FO) membranes. The composite membranes were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR), Water contact angle (WCA), Zeta potential and confocal laser scanning microscopic (CLSM). In the FO filtration experiment, the membrane performance of TFC-1 with 1 M sodium chloride solution as the draw solution and deionized water as the feed solution was the best, with the water flux of 25.54 ± 0.7 L m-2 h-1 and the reverse salt flux of 4.7 ± 0.4 g m-2 h-1. Although the hydrogel coating produced a certain hydraulic resistance, the flux of the modified membrane was only reduced by about 8%, compared with the unmodified membrane. However, the anti-bacterial property (Pseudomonas aeruginosa) and anti-fouling properties (bovine serum protein and lysozyme protein) of the modified membranes were improved, showing good antibacterial properties (99%) and flux recovery rate (over 90%). The modified method has the advantages of easy access to raw materials, simple operation and no risk of secondary pollution, which can effectively reduce the cost of chemical cleaning and extend the service life of the membrane. The modification of membrane by chitosan-based hydrogel is a promising option in the field of membrane anti-bacteria.

Occurrence and Health Risk Assessment of Sulfonamide Antibiotics in Different Freshwater Fish in Northeast China.

This study aimed to investigate the levels of 12 sulfonamide antibiotics in freshwater fish species obtained from three cities in northeastern China (Harbin, Changchun, and Shenyang). The analysis was conducted using HPLC-MS/MS to accurately quantify the antibiotic concentrations in the fish samples. The results showed that the average levels of sulfonamide antibiotics in fish samples from Harbin, Changchun, and Shenyang were 1.83 ng/g ww, 0.98 ng/g ww, and 1.60 ng/g ww, respectively. Sulfamethoxazole displayed the highest levels and detection rates in all three cities, whereas sulphapyridine exhibited the lowest concentrations in all the fish samples. The levels of sulfonamide antibiotic residues in the different fish species varied widely among the cities, and the highest level of antibiotic residues was found in the muscle of carnivorous fish. The results from a health risk evaluation on the consumption of these fish indicated that the risk from long-term antibiotic exposure to local residents from the intake of the sampled fish was small and not sufficient to pose a significant health risk to consumers.

Identification of a novel combination treatment strategy in clear cell renal cell carcinoma stem cells with shikonin and ipilimumab.

Background: Management of clear cell renal cell carcinoma (ccRCC) has changed rapidly in recent years with the advent of immune checkpoint inhibitors (ICIs). However, only a limited number of patients can sustainably respond to immune checkpoint inhibitors and many patients develop resistance to therapy, creating an additional need for therapeutic strategies to improve the efficacy of systemic therapies. Methods: Binding probability and target genes prediction using online databases, invasion, migration, and apoptosis assays as well as the inhibition of cancer stem cells (CSCs) markers in ccRCC cell lines were used to select the most promising phytochemicals (PTCs). Mixed lymphocyte tumor cell culture (MLTC) system and flow cytometry were performed to confirm the potential combination strategy. The potential immunotherapeutic targets and novel CSC markers were identified via the NanoString analysis. The mRNA and protein expression, immune signatures as well as survival characteristics of the marker in ccRCC were analyzed via bioinformation analysis. Results: Shikonin was selected as the most promising beneficial combination partner among 11 PTCs for ipilimumab for the treatment of ccRCC patients due to its strong inhibitory effect on CSCs, the significant reduction of FoxP3+ Treg cells in peripheral blood mononuclear cells (PBMCs) of patients and activation of the endogenous effector CD3+CD8+ and CD3+CD4+ T cells in response to the recognition of tumor specific antigens. Based on NanoString analysis VCAM1, CXCL1 and IL8 were explored as potential immunotherapeutic targets and novel CSC markers in ccRCC. The expression of VCAM1 was higher in the tumor tissue both at mRNA and protein levels in ccRCC compared with normal tissue, and was significantly positively correlated with immune signatures and survival characteristics in ccRCC patients. Conclusion: We propose that a combination of shikonin and ipilimumab could be a promising treatment strategy and VCAM1 a novel immunotherapeutic target for the treatment of ccRCC.

SEVERE BURN-INDUCED MITOCHONDRIAL RECRUITMENT OF CALPAIN CAUSES ABERRANT MITOCHONDRIAL DYNAMICS AND HEART DYSFUNCTION.

ABSTRACT: Mitochondrial damage is an important cause of heart dysfunction after severe burn injury. However, the pathophysiological process remains unclear. This study aims to examine the mitochondrial dynamics in the heart and the role of µ-calpain, a cysteine protease, in this scenario. Rats were subjected to severe burn injury treatment, and the calpain inhibitor MDL28170 was administered intravenously 1 h before or after burn injury. Rats in the burn group displayed weakened heart performance and decreased mean arterial pressure, which was accompanied by a diminishment of mitochondrial function. The animals also exhibited higher levels of calpain in mitochondria, as reflected by immunofluorescence staining and activity tests. In contrast, treatment with MDL28170 before any severe burn diminished these responses to a severe burn. Burn injury decreased the abundance of mitochondria and resulted in a lower percentage of small mitochondria and a higher percentage of large mitochondria. Furthermore, burn injury caused an increase in the fission protein DRP1 in the mitochondria and a decrease in the inner membrane fusion protein OPA1. Similarly, these alterations were also blocked by MDL28170. Of note, inhibition of calpain yielded the emergence of more elongated mitochondria along with membrane invagination in the middle of the longitude, which is an indicator of the fission process. Finally, MDL28170, administered 1 h after burn injury, preserved mitochondrial function and heart performance, and increased the survival rate. Overall, these results provided the first evidence that mitochondrial recruitment of calpain confers heart dysfunction after severe burn injury, which involves aberrant mitochondrial dynamics.

WITHDRAWN: RNA binding protein Musashi2 regulates dairy cows' mastitis by activating the TGFß signaling pathway.

This article has been withdrawn at the request of the editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

A gene-based association test of interactions for maternal-fetal genotypes identifies genes associated with nonsyndromic congenital heart defects.

The risk of congenital heart defects (CHDs) may be influenced by maternal genes, fetal genes, and their interactions. Existing methods commonly test the effects of maternal and fetal variants one-at-a-time and may have reduced statistical power to detect genetic variants with low minor allele frequencies. In this article, we propose a gene-based association test of interactions for maternal-fetal genotypes (GATI-MFG) using a case-mother and control-mother design. GATI-MFG can integrate the effects of multiple variants within a gene or genomic region and evaluate the joint effect of maternal and fetal genotypes while allowing for their interactions. In simulation studies, GATI-MFG had improved statistical power over alternative methods, such as the single-variant test and functional data analysis (FDA) under various disease scenarios. We further applied GATI-MFG to a two-phase genome-wide association study of CHDs for the testing of both common variants and rare variants using 947 CHD case mother-infant pairs and 1306 control mother-infant pairs from the National Birth Defects Prevention Study (NBDPS). After Bonferroni adjustment for 23,035 genes, two genes on chromosome 17, TMEM107 (p = 1.64e-06) and CTC1 (p = 2.0e-06), were identified for significant association with CHD in common variants analysis. Gene TMEM107 regulates ciliogenesis and ciliary protein composition and was found to be associated with heterotaxy. Gene CTC1 plays an essential role in protecting telomeres from degradation, which was suggested to be associated with cardiogenesis. Overall, GATI-MFG outperformed the single-variant test and FDA in the simulations, and the results of application to NBDPS samples are consistent with existing literature supporting the association of TMEM107 and CTC1 with CHDs.

A retrospective study for association between post-transfusion hemoglobin S level and pre-transfusion hemoglobin S level at the next scheduled transfusion.

BACKGROUND: Patients with sickle cell disease (SCD) frequently undergo prophylactic red blood cell (RBC) exchange transfusion and simple transfusion (RCE/T) to prevent complications of disease, such as stroke. These treatment procedures are performed with a target hemoglobin S (HbS) of ≤30%, or a goal of maintaining an HbS level of <30% immediately prior to the next transfusion. However, there is a lack of evidence-based instructions for how to perform RCE/T in a way that will result in an HbS value <30% between treatments. PRINCIPAL OBJECTIVE: To determine whether targets for post-treatment HbS (post-HbS) or post-treatment HCT (post-HCT) can help to maintain an HbS <30% or <40% between treatments. MATERIALS AND METHODS: We performed a retrospective study of patients with SCD treated with RCE/T at Montefiore Medical Center from June 2014 to June 2016. The analysis included patients of all ages, and data including 3 documented parameters for each RCE/T event: post-HbS, post-HCT, and follow-up HbS (F/u-HbS), which is the pre-treatment HbS prior to the next RCE/T. Generalized linear mixed model was used for estimating the association between post-HbS or post-HCT levels and F/u-HbS <30%. RESULTS: Based on our results, targeting post-HbS ≤10% was associated with higher odds of having events of F/u-HbS <30% between monthly treatments. Targeting post-HbS ≤15% was associated with higher odds of events of F/u-HbS < 40%. As compared to post-HCT ≤30%, a post-HCT >30%-36% did not contribute to more F/u-HbS <30% or HbS <40% events. CONCLUSIONS: For patients with SCD undergoing regular RCE/T for stroke prevention, a post-HbS ≤10% can be used as a goal to help maintain an HbS <30% for 1 month, and a post-HbS ≤15% allowed patients to maintain HbS <40%.

Does Incident Cardiovascular Disease Lead to Greater Odds of Functional and Cognitive Impairment? Insights From the Health and Retirement Study.

BACKGROUND: Although studies to date have broadly shown that cardiovascular disease (CVD) increases cognitive and physical impairment risk, there is still limited understanding of the magnitude of this risk among relevant CVD subtypes or age cohorts. METHODS: We analyzed longitudinal data from 16 679 U.S. Health and Retirement Study participants who were aged ≥65 years at study entry. Primary endpoints were physical impairment (activities of daily living impairment) or cognitive impairment (Langa-Weir Classification of dementia). We compared these endpoints among participants who developed incident CVD versus those who were CVD free, both in the short term (<2-year postdiagnosis) and long term (>5 years), controlling for sociodemographic and health characteristics. We then analyzed the effects by CVD subtype (atrial fibrillation, congestive heart failure, ischemic heart disease, and stroke) and age-at-diagnosis (65-74, 75-84, and ≥85). RESULTS: Over a median follow-up of 10 years, 8 750 participants (52%) developed incident CVD. Incident CVD was associated with significantly higher adjusted odds (aOR) of short-term and long-term physical and cognitive impairment. The oldest (≥85) age-at-diagnosis subgroup had the highest risk of short-term physical (aOR 3.01, 95% confidence interval [CI]: 2.40-3.77) and cognitive impairment (aOR 1.96, 95% CI: 1.55-2.48), as well as long-term impairment. All CVD subtypes were associated with higher odds of physical and cognitive impairment, with the highest risk for patients with incident stroke. CONCLUSIONS: Incident CVD was associated with an increased risk of physical and cognitive impairment across CVD subtypes. Impairment risk after CVD was highest among the oldest patients (≥85 years) who should therefore remain a target for prevention efforts.

SERPINB7 mutation causes Nagashima-type palmoplantar keratosis and its spatiotemporal expression in zebrafish.

Serine protease inhibitor B7 (SERPINB7) mutations have been reported to cause Nagashima-type palmoplantar keratosis (NPPK), but their biological effects are largely unknown. We conducted whole-exome sequencing and identified a c.796C>T (p.Arg266Ter) mutation in SERPINB7 in a Chinese pedigree, which presented as an autosomal recessive inheritance pattern. We assessed the function of SERPINB7 in homozygous and heterozygous mutation carriers, and the results suggested that the single c.796C>T mutation may alter the subcellular localization of SERPINB7. One of the homozygous mutation patients (II-3) was treated with ixekizumab and showed moderate improvement in keratinization. In addition, we analysed the spatiotemporal expression of serpinb1l1 and serpinb1l3, the zebrafish homologue of human SERPINB7, which is expressed in larvae and adults. In larvae, both serpinb1l1 and serpinb1l3 were expressed in the digestive tract. Then, we performed RT-PCR on adult fins based on similarity to the site of NPPK expression in humans and found that the genes were expressed in five fins (pectoral, pelvic, dorsal, anal and caudal) of the zebrafish distal extremity. Taken together, our results demonstrated that the single c.796C>T (p.Arg266Ter) mutation may alter the location of SERPINB7-encoded protein in the skin, while zebrafish SERPINB7 homologue was expressed in adult fins. These findings will enable us to construct knock-out models to explore the pathogenesis of palmoplantar keratosis.

Predicting of motor vehicle carbon emissions and spatio-temporal characteristic analysis in the Beijing-Tianjin-Hebei region.

In China, road traffic carbon emissions and their share in total carbon emissions have significantly increased. In the context of double carbon, the Beijing-Tianjin-Hebei region, the largest urban agglomeration in northern China, is receiving more and more attention. Due to the unbalanced development in Beijing-Tianjin-Hebei urban agglomeration, this thesis presents three computational models to calculate road traffic carbon emissions for large, medium-sized, and small cities and intercity traffic arteries based on the road network. The results show that in 2019, Beijing has the highest road carbon emissions reaching 19.91 million t CO2 which is almost three times that of Shijiazhuang, the capital city of Hebei province. Dwellers' commuting usually results in an increase of 2.9%, 3.3%, and 4.5% on weekdays compared with weekends for Tianjin, Shijiazhuang, and Beijing, respectively. As for the intercity road, the daily traffic flow is about 1.92 million vehicles, leading to total carbon emissions of 22.97 million t CO2. In addition, the reduction potential of carbon emissions in Beijing is evaluated. If the average road speed is increased to 0.9Vf (road design speed) during the morning rush hour in Beijing from 7 a.m. to 8 a.m., the road emission reduction could reach 57.85%.