Elemental and particle size fractionation during the transport of Eu(III)-silicate colloids in water-saturated porous media.

Actinides (An)-bearing colloids could facilitate An migration in the environment. However, little is known about the transport behavior of An(III)-silicate colloids, which are readily formed by the reaction of An3+ with silicic acid under environmental conditions. Column experiments were conducted to investigate the transport of Eu(III)-silicate colloids (chemical analog of An(III)-silicate colloids) in water-saturated porous media as a function of pH, ionic strength (IS) and the presence of fulvic acid (FA). The results showed that colloid transport was more favorable at relatively low IS (≤ 50 mM) and high pH levels (pH ≥ 7). The presence of FA (5-10 mg/L) significantly enhanced the colloid transport. Under high IS (≥ 100 mM), the transport feature of colloids was turned from blocking to ripening due to the on-going aggregation of colloids. Additionally, an interesting elemental fractionation, i.e., a discrepancy in the breakthrough curves (BTCs) with respect to the C/C0 values of Si and Eu, was observed in the IS of 100-500 mM. A detailed investigation indicated that the elemental fractionation could be attributed to the partial Si dissolution of the colloids, the heterogeneity of the colloid size and element composition, and particle size fractionation during colloid transport. Extended Derjaguin-Landau-Verwey-Overbeek interaction energy calculations and convective-dispersive equation modeling were performed to illustrate variations in the colloid transport profiles. These findings illustrate the importance of Si dissolution in the migration of metal-silicate colloids and highlight the significant influence of the heterogeneity of colloid size and composition on the transport/migration behavior of colloids in the environment.

Graphitic carbon @ silver nanoparticle @ porous silicon Bragg mirror composite SERS substrate for gallic acid detection.

Graphite carbon (G) @ silver (Ag) @ porous silicon Bragg mirror (PSB) composite SERS substrate was successfully synthesized using electrochemical etching (ec) and hydrothermal carbonization (HTC) techniques with silver nitrate as the source of silver and glucose as the source of carbon. The PSB was used as a functional scaffold for the synthesis of graphite-carbon and silver composite nanoparticles (G@AgNPs) on its surface, thereby combining SERS activity and antioxidant properties. To our knowledge, this is the first time that G@AgNPs has been synthesized on the PSB using glucose as a carbon source. The synthesized G@Ag@PSB was utilized as a SERS platform for the detection of gallic acid (GA). Test results demonstrated that the substrate exhibited a remarkable SERS enhancement capability for GA, with the enhancement factor (EF) reaching 2 × 105. The reproducibility of the SERS spectral signal was excellent, with a relative standard deviation (RSD) of 7.5 %. The sensitivity test results showed that the linear range of GA detection based on G@Ag@PSB composite SERS substrate was 2 × 10-3-2 × 10-12M. The relationship between GA concentration and SERS signal intensity exhibited a strong linear correlation, with a linear correlation coefficient (R2) of 0.97634. Moreover, even with an extended storage period, only a marginal decline in the signal intensity of GA on the substrate was observed. The results of this study demonstrate that the prepared G@Ag@PSB composite SERS substrate had good potential application performance as a low-cost SERS detection platform suitable for commercial use. In addition, this advance facilitates the further exploration of more nanomaterials with ultra-high sensitivity in SERS technology.

Structures of African swine fever virus topoisomerase complex and their implications.

African swine fever virus (ASFV) is the causal agent of African swine fever (ASF), which is contagious and highly lethal to domestic pigs and wild boars. The genome of ASFV encodes many proteins important for ASFV life cycle. The functional importance of topoisomerase AsfvTopII has been confirmed by in vivo and in vitro assays, but the structure of AsfvTopII is poorly studied. Here, we report four AsfvTopII complex structures. The ATPase domain structures reveal the detailed basis for ATP binding and hydrolysis, which is shared by AsfvTopII and eukaryotic TopIIs. The DNA-bound structures show that AsfvTopII follows conserved mechanism in G-DNA binding and cleavage. Besides G-DNA, a T-DNA fragment is also captured in one AsfvTopII structure. Mutagenesis and in vitro assays confirm that Pro852 and the T-DNA-binding residue Tyr744 are important for the function of AsfvTopII. Our study not only advances the understanding on the biological function of AsfvTopII, but also provides a solid basis for the development of AsfvTopII-specific inhibitors.

First-line treatment of severe aplastic anemia: immunosuppressive therapy plus eltrombopag versus haploidentical hematopoietic stem cell transplantation, a multicenter prospective study.

Matched-related donor hematopoietic stem cell transplantation (HSCT) remains the preferred first-line option for severe aplastic anemia (SAA) patients aged <40 years even in the era of eltrombopag (EPAG). However, there has not been any direct comparison between immunosuppressive therapy (IST) plus EPAG (IST + EPAG) and haploidentical HSCT (Haplo-HSCT) as first-line therapy. This study prospectively compared the efficacy, safety and health-related quality of life (HRQoL) of Haplo-HSCT (n = 147) and IST + EPAG (n = 121) as first-line treatment for patients with SAA. The results showed that 86.3% of patients in the Haplo-HSCT group and 24.1% of patients in the IST + EPAG group achieved normal complete blood count (CBC) (P < 0.001) after 6 months of treatment. The time to achieve transfusion independence and absolute neutrophil count ≥ 1.0 × 109/L were shorter in the Haplo-HSCT group than in the IST + EPAG group (P < 0.05). In the IST + EPAG and Haplo-HSCT, 3-year overall survival (OS) was 92.4 ± 2.4% and 82.8 ± 3.1% (P = 0.017), whereas 3-year failure-free survival (FFS) was 69.4 ± 4.2% and 81.6 ± 3.2% (P = 0.002), respectively. Similar results were observed in patients with <40 years of age. Among patients with ≥40 years of age, there was no difference in 3-year OS (88.6 ± 4.8% vs. 82.4 ± 8.1%, P = 0.517) between the IST + EPAG and Haplo-HSCT groups, whereas 3-year FFS was lower in the IST + EPAG (58.7 ± 7.5% vs. 82.4 ± 8.1%, P = 0.043). Subgroup analysis for populations aged <40 years indicated that SAA benefited more from IST + EPAG, and very SAA (vSAA) benefited more from Haplo-HSCT. Patients treated with haplo-HSCT scored significantly better in the HRQoL than treated with IST + EPAG (P < 0.0001). Multivariate analysis showed that first-line Haplo-HSCT was associated with normal CBC at 6 months, better FFS and led to a better HRQoL (P < 0.001). In summary, the IST + EPAG achieved better OS for <40 years SAA patients, while the Haplo-HSCT accelerated hematopoietic recovery and HRQoL, achieved better FFS even for those <40 years vSAA and ≥40 years patients.

The role of radiotherapy in the treatment of sinonasal undifferentiated carcinoma: A population-based analysis.

BACKGROUND: Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive disease with ambiguous management and poor prognosis. This study aimed to evaluate the role of radiation therapy (RT) and explore the optimal treatment sequence. METHODS: Retrospective analysis of survival trends of 410 SNUC patients between 1973 and 2015. RESULTS: The 5-year cancer-specific survival (CSS) rate (45.1%) and overall survival (OS) rates (38.1%) were reported in the 84-month median follow-up. Radiotherapy was a prognosticator for improving CSS (hazard ratio [HR] = 0.425, 95% confidence interval [CI]: 0.299-0.603, p = 0.000) and OS (HR = 0.415, 95% CI: 0.303-0.570, p = 0.000), either with surgery (p = 0.000) or without surgery (p = 0.000). However, in a combined therapy of surgery and RT, preoperative and postoperative RT (5-year OS rates were 47.1% and 45.6%, respectively, p = 0.486) were not significantly different. CONCLUSIONS: Radiotherapy plays a key role in improving SNUC survival rates. No significant difference in survival rates was observed in preoperative and postoperative RT treatment.

High-Entropy-Inspired Multicomponent Electrical Double Layer Structure Design for Stable Zinc Metal Anodes.

Regulating the electrical double layer (EDL) structure can enhance the cycling stability of Zn metal anodes, however, the effectiveness of this strategy is significantly limited by individual additives. Inspired by the high-entropy (HE) concept, we developed a multicomponent (MC) EDL structure composed of La3+, Cl-, and BBI anions by adding dibenzenesulfonimide (BBI) and LaCl3 additives into ZnSO4 electrolytes (BBI/LaCl3/ZnSO4). Specifically, La3+ ions accumulate within EDL to shield the net charges on the Zn surface, allowing more BBI anions and Cl- ions to enter this region. Consequently, this unique MC EDL enables Zn anodes to simultaneously achieve uniform electric field, robust SEI layer, and balanced reaction kinetics. Moreover, the synergistic parameter-a novel descriptor for quantifying collaborative improvement-was first proposed to demonstrates the synergistic effect between BBI and LaCl3 additives. Benefitting from these advantages, Zn metal anodes achieved a high reversibility of 99.5% at a depth of discharge (DoD) of 51.3%, and Zn|MnO2 pouch cells exhibited a stable cycle life of 100 cycles at a low N/P ratio of 2.9.

The Influence of Body Fat Dynamics on Pulmonary Immune Responses in Murine Tuberculosis: Unraveling Sex-Specific Insights.

The World Health Organization (WHO) highlights a greater susceptibility of males to tuberculosis (TB), a vulnerability attributed to sex-specific variations in body fat and dietary factors. Our study delves into the unexplored terrain of how alterations in body fat influence Mycobacterium tuberculosis (Mtb) burden, lung pathology, immune responses, and gene expression, with a focus on sex-specific dynamics. Utilizing a low-dose Mtb-HN878 clinical strain infection model, we employ transgenic FAT-ATTAC mice with modulable body fat to explore the impact of fat loss (via fat ablation) and fat gain (via a medium-fat diet, MFD). Firstly, our investigation unveils that Mtb infection triggers severe pulmonary pathology in males, marked by shifts in metabolic signaling involving heightened lipid hydrolysis and proinflammatory signaling driven by IL-6 and localized pro-inflammatory CD8+ cells. This stands in stark contrast to females on a control regular diet (RD). Secondly, our findings indicate that both fat loss and fat gain in males lead to significantly elevated (1.6-fold (p ≤ 0.01) and 1.7-fold (p ≤ 0.001), respectively) Mtb burden in the lungs compared to females during Mtb infection (where fat loss and gain did not alter Mtb load in the lungs). This upsurge is associated with impaired lung lipid metabolism and intensified mitochondrial oxidative phosphorylation-regulated activity in lung CD8+ cells during Mtb infection. Additionally, our research brings to light that females exhibit a more robust systemic IFNγ (p ≤ 0.001) response than males during Mtb infection. This heightened response may either prevent active disease or contribute to latency in females during Mtb infection. In summary, our comprehensive analysis of the interplay between body fat changes and sex bias in Mtb infection reveals that alterations in body fat critically impact pulmonary pathology in males. Specifically, these changes significantly reduce the levels of pulmonary CD8+ T-cells and increase the Mtb burden in the lungs compared to females. The reduction in CD8+ cells in males is linked to an increase in mitochondrial oxidative phosphorylation and a decrease in TNFα, which are essential for CD8+ cell activation.

Correlation between Serum 25 (OH) D Levels with Insulin Resistance and Metabolic Associated Fatty Liver Disease - A Retrospective Study based on Chinese Patients with Newly Diagnosed Type 2 Diabetes Mellitus.

AIMS: The objective of this study was to investigate the correlation between serum 25 hydroxyvitamin D [25(OH)D] levels and insulin resistance, as well as metabolic associated fatty liver disease (MAFLD) in newly diagnosed with type 2 diabetes mellitus(T2DM) patients. METHOD: A retrospective analysis was conducted on 491 T2DM patients who were newly diagnosed between January 2017 and August 2022 at Peking University International Hospital. These patients were categorized into three groups based on their 25(OH)D levels. RESULTS: The prevalence of MAFLD was significantly elevated in both the Vitamin D(VD) deficiency group and the VD insufficiency group compared to the VD sufficiency group (χ2 = 6.51, p<0.05). The patients in the VD sufficiency group had lower levels of insulin resistance，as assessed by the homeostasis model assessment when compared to the VD deficiency group and the VD insufficiency group (F = 8.61，p < 0.05). Additionally, the VD sufficiency group demonstrated higher levels of ß cell function in comparison to the other two groups(p<0.05， respectively). (2) A significant negative correlation was observed between 25(OH)D levels and insulin resistance, as assessed by the homeostasis model assessment in T2DM patients(r=-0.33，p<0.05 for females; r=-0.32，p<0.05 for males). (3) In male patients, 25(OH)D was identified as a protective factor against MAFLD(OR = 0.42;95%CI:0.19-0.95;p<0.05). Meanwhile，in female patients, 25(OH)D was also associated with a reduced risk of MAFLD(OR = 0.35;95%CI 0.17-0.89;p<0.05). Additionally, the study determined that the threshold values for 25(OH)D were 15.06 ng/ml in female patients and 18.79 ng/ml in male patients for predicting MAFLD. CONCLUSION: In newly diagnosed with T2DM patients, the level of 25(OH)D may be related to insulin resistance and ß cell secretion function independently and VD deficiency is an independent risk factor for MAFLD in patients with newly diagnosed T2DM.

A phase III randomized clinical trial comparing laparoscopic radical hysterectomy based on open state with abdominal radical hysterectomy in patients with early-stage cervical cancer.

BACKGROUND: Cervical cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women, The standard treatment recommendation for women with early cervical cancer is radical hysterectomy with pelvic lymph node dissection, however, articles published in recent years have concluded that the treatment outcome of laparoscopic surgery for cervical cancer is inferior to that of open surgery. Thus, we choose a surgically new approach; the laparoscopic cervical cancer surgery in the open state is compared with the traditional open cervical cancer surgery, and we hope that patients can still have a good tumor outcome and survival outcome. This trial will investigate the effectiveness of laparoscopic cervical cancer surgery in the open-state treatment of early-stage cervical cancer. METHOD AND DESIGN: This will be an open-label, 2-armed, randomized, phase-III single-center trial of comparing laparoscopic radical hysterectomy based on open state with abdominal radical hysterectomy in patients with early-stage cervical cancer. A total of 740 participants will be randomly assigned into 2 treatment arms in a 1:1 ratio. Clinical, laboratory, ultrasound, and radiology data will be collected at baseline, and then at the study assessments and procedures performed at baseline and 1 week, 6 weeks, and 3 months, and follow-up visits begin at 3 months following surgery and continue every 3 months thereafter for the first 2 years and every 6 months until year 4.5. The primary aim is the rate of disease-free survival at 4.5 years. The secondary aims include treatment-related morbidity, costs and cost-effectiveness, patterns of recurrence, quality of life, pelvic floor function, and overall survival. CONCLUSIONS: This prospective trial aims to show the equivalence of the laparoscopic cervical cancer surgery in the open state versus the transabdominal radical hysterectomy approach for patients with early-stage cervical cancer following a 2-phase protocol. TRIAL REGISTRATION: ChiCTR2300075118. Registered on August 25, 2023.

Proximal Femoral Metastasis From Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma Mimicking Osteosarcoma on Magnetic Resonance Imaging.

The aggressive nature of lung cancer is frequently accompanied by a high incidence of bone metastasis; however, proximal femoral metastasis from lung cancer is comparatively uncommon when compared to other malignancies. In this report, we present the case of a 53-year-old Asian male who presented with pain in the left thigh and back. Magnetic resonance imaging revealed severe bone destruction with involvement of adjacent soft tissue mass at the left thigh, exhibiting imaging findings that mimic osteosarcoma. Subsequent bone biopsy confirmed the diagnosis of epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma with bone metastasis. The patient achieved survival following administration of osimertinib and underwent surgery for femoral metastases without palliative surgery for lung cancer. Therefore, proximal femoral metastasis from EGFR-mutated lung adenocarcinoma should be considered as a differential diagnosis in patients suspected to have osteosarcoma. The imaging findings of proximal femoral metastasis from EGFR-mutated lung adenocarcinoma were presented, and their therapeutic management was discussed.

Opportunities and Challenges in the Development of Antibody-Drug Conjugate for Triple-Negative Breast Cancer: The Diverse Choices and Changing Needs.

Triple-negative breast cancer (TNBC) is a highly heterogeneous breast cancer subtype, which is also characterized by the aggressive phenotype, high recurrence rate, and poor prognosis. Antibody-drug conjugate (ADC) is a monoclonal antibody with a cytotoxic payload connected by a linker. ADC is gaining more and more attention as a targeted anti-cancer agent. Clinical studies of emerging ADC drugs such as sacituzumab govitecan and trastuzumab deruxtecan in patients with metastatic breast cancer (including TNBC) are progressing rapidly. In view of its excellent clinical efficacy and good tolerability, Sacituzumab govitecan gained accelerated approval by the FDA for the treatment of advanced metastatic TNBC in 2020. This review discusses the treatment status and challenges in TNBC, with an emphasis on the current status of ADC development and clinical trials in TNBC and metastatic breast cancer. We also summarize the clinical experience and future exploration directions of ADC development for TNBC patients.

Luspatercept enhances hemoglobin levels in a Chinese boy with congenital sideroblastic anemia: A case report.

BACKGROUND: Congenital sideroblastic anemia (CSA) is a rare and heterogeneous group of genetic disorders. Conventional treatment include pyridoxine (vitamin B6) and allogeneic hematopoietic stem cell transplantation (allo-HSCT), and can alleviate anemia in the majority of cases. Nevertheless, some CSA cases remain unresponsive to pyridoxine or are unable to undergo allo-HSCT. Novel management approaches is necessary to be developed. To explore the response of luspatercept in treating congenital sideroblastic anemia. CASE SUMMARY: We share our experience in luspatercept in a 4-year-old male patient with CSA. Luspatercept was administered subcutaneously at doses of 1.0 mg/kg/dose to 1.25 mg/kg/dose every 3 wk, three consecutive doses, evaluating the hematological response. Luspatercept leading to a significant improvement in the patient's anemia. The median hemoglobin during the overall treatment with three doses of luspatercept was 90 (75-101) g/L, the median absolute reticulocyte count was 0.0593 (0.0277-0.1030) × 1012/L, the median serum ferritin was 304.3 (234.4-399) ng/mL, and the median lifespan of mature red blood cells was 80 (57-92) days. Notably, no adverse reactions, such as headaches, dizziness, vomiting, joint pain, or back pain, were observed during the treatment period. CONCLUSION: We believe that luspatercept might emerge as a viable therapeutic option for the maintenance treatment of CSA or as a bridging treatment option before hematopoietic stem cell transplantation.

PCMD: A multilevel comparison database of intra- and cross-species metabolic profiling in 530 plant species.

Comparative metabolomics plays a crucial role in investigating gene function, exploring metabolite evolution, and accelerating crop genetic improvement. However, a systematic platform for comparing intra- and cross-species metabolites is currently lacking. Here, we report the Plant Comparative Metabolome Database (PCMD; http://yanglab.hzau.edu.cn/PCMD), a multilevel comparison database based on predicted metabolic profiles in 530 plant species. PCMD serves as a platform for comparing metabolite characteristics at various levels, including species, metabolites, pathways, and biological taxonomy. The database also provides a series of user-friendly online tools, such as Species-comparison, Metabolites-enrichment, and ID conversion, enabling users to perform comparisons and enrichment analyses of metabolites across different species. In addition, PCMD establishes a unified system based on existing metabolite-related databases by standardizing metabolite numbering. PCMD is the most species-rich comparative plant metabolomics database currently available, and a case study demonstrated its capability to provide new insights into understanding plant metabolic diversity.

B7-H3 enhances colorectal cancer progression by regulating HB-EGF via HIF-1α.

Background: B7-H3 (or CD276) represents an important costimulatory molecule expressed in many malignant solid tumors, including colorectal cancer (CRC). The receptor of B7-H3 is not known, and the intracellular function of B7-H3 remains obscure. Herein, we report that B7-H3 upregulated the epidermal growth factor heparin-binding epidermal growth factor (HB-EGF), likely by regulating hypoxia-inducible factor 1α (HIF-1α) and thereby promoting the progression of CRC. Methods: Lentiviral transfection was performed on CRC cells to establish stable low-B7-H3 expression cells. A mechanistic analysis with an Agilent human gene expression profiling chip was conducted on them. Clinical data and specimens were collected to detect the connection between B7-H3 and HB-EGF in CRC. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect the messenger RNA (mRNA) level of B7-H3, HB-EGF, and HIF-1α. Chromatin immunoprecipitation (ChIP) quantitative real-time PCR was conducted. The protein level of HIF-1α and the phosphatidylinositide 3-kinases (PI3K)-protein kinase B (AKT) pathway were detected by western blot. HIF-1α was recovered by lentiviral transfection, and the HB-EGF mRNA levels, proliferation, invasion, and angiogenesis ability were detected. Results: B7-H3 promoted tumor progression through HB-EGF and the PI3K-AKT pathway. As B7-H3 was downregulated, HB-EGF levels were significantly reduced simultaneously, a growth trend that was shown by both CRC cell lines and cancer tissues. In addition, B7-H3 and HB-EGF had significant associations with tumor-node-metastasis (TNM) stage and lymph node metastasis in 50 CRC patients. The binding ability of HIF-1α to the HB-EGF promoter region was significantly decreased in the shB7-H3 RKO group. Western blot revealed that PI3K, AKT, and mammalian target of rapamycin (mTOR) protein amounts and p-AKT and p-mTOR phosphorylation were also downregulated in shB7-H3 RKO cells, suggesting that B7-H3 may regulate HIF-1α via PI3K-AKT signaling. After recovery of the HIF-1α level by lentiviral transfection, the HB-EGF mRNA levels, proliferation, invasion, and angiogenesis in CRC cells recovered as well. Conclusions: B7-H3 may transmit intracellular signals through PI3K-AKT-mTOR-HIF-1α signaling, upregulating HB-EGF. As the final transcription factor of the pathway, HIF-1α regulates the transcription of the HB-EGF gene, thereby promoting HB-EGF expression, which eventually mediates cell proliferation, invasion, and angiogenesis and promotes the progression of CRC.

Remnant cholesterol is associated with the progression and regression of metabolic dysfunction-associated steatotic liver disease in Chinese adults.

BACKGROUND: The aim of this study was to explore the associations of serum remnant cholesterol (RC) levels with the progression and regression of metabolic dysfunction-associated steatotic liver disease (MASLD) in Chinese adults. METHODS: We conducted a cross-sectional study in 13,903 individuals who underwent transient elastography tests (cohort 1) and a longitudinal study in 17,752 individuals who underwent at least two health check-up exams with abdominal ultrasound (cohort 2). Anthropometric and biochemical parameters were collected. Serum RC levels were calculated. Noninvasive fibrosis indices such as FIB-4 were evaluated in cohort 2. RESULTS: In cohort 1, serum RC levels were positively and independently associated with the severity of hepatic steatosis and liver fibrosis according to logistic regression analysis. In cohort 2, baseline serum RC levels were increased in participants with the incidence of MASLD and decreased in participants with the regression of MASLD during the follow-up period. Baseline serum RC levels were independently associated with an increased risk of development and a decreased likelihood of regression of MASLD: the fully adjusted hazard ratios (HR) were 2.785 (95 % CI 2.332-3.236, P < 0.001) and 2.925 (95 % CI 2.361-3.623, P < 0.001), respectively. In addition, when we used FIB-4 to evaluate liver fibrosis, baseline serum RC levels were positively correlated with the incidence of high-intermediate probability of advanced fibrosis. However, we did not find an association between serum RC levels and the regression of liver fibrosis. CONCLUSION: Serum RC levels are independently correlated with the progression and regression of MASLD in Chinese adults, suggesting that RC may participate in the pathophysiological process of MASLD.

Association between organophosphate esters exposure and all-cause and cause-specific mortality: a national population-based cohort study.

Exposure to organophosphate esters (OPEs) is associated with several chronic diseases, but the relationship with mortality risk is unclear. Therefore, we used the National Health and Nutrition Examination Survey 2011-2018 data to evaluate these relationships. 6,869 participants aged 18 years or older were included. Survival status information was obtained through the National Death Index through 31 December 2019. Multivariable COX regression model was adopted to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationships of urinary OPEs metabolites with mortality risk. During an average of 5.0 years of follow-up, 406 deaths were documented. After adjusting for confounders, bis(2-chloroethyl) phosphate was associated with an increased risk of all-cause mortality [HR (95%CI) = 1.12(1.05-1.20)] and cardiovascular mortality [HR (95%CI) = 1.15(1.04-1.26)]. Our study found that exposure to OPEs was significantly associated with increased risks of all-cause and cardiovascular mortality. Consequently, controlling OPEs exposure is needed to alleviate the health-related burden.

Mapping Theme Trends and Research Frontiers in Dexmedetomidine Over Past Decade: A Bibliometric Analysis.

Background: Dexmedetomidine, an α2-adrenergic receptor (α2-AR) agonist, is extensively used in clinical and animal studies owing to its sedative, analgesic, and anxiolytic effects. The diverse range of research domains associated with dexmedetomidine poses challenges in defining pivotal research directions. Therefore, this study aimed to conduct a qualitative and quantitative bibliometric study in the field of dexmedetomidine over the past decade to establish current research trends and emerging frontiers. Methods: Relevant publications in the field of dexmedetomidine between 2014 and 2023 were extracted from the Web of Science Core Collection database. The bibliometric analysis, incorporating statistical and visual analyses, was conducted using CiteSpace (6.1.R6) and R (4.3.1). Results: The present study encompassed a total of 5,482 publications, exhibiting a consistent upward trend over the past decade. The United States and its institutions had the highest centrality. Ji, Fuhai, and Ebert, Thomas J. were identified as the most productive author and the most cited author, respectively. As anticipated, the most cited journal was Anesthesiology. Moreover, cluster analysis of cited references and co-occurrence of keywords revealed that recent studies were primarily focused on sedation, delirium, and opioid-free anesthesia. Finally, a timeline view of keywords clusters and keywords burst demonstrated that primary research frontiers were stress response, neuroinflammation, delirium, opioid-free anesthesia, peripheral nerve block, and complications. Conclusion: Current research trends and directions are focused on sedation, delirium, and opioid-free anesthesia, as evidenced by our results. The frontier of future research is anticipated to encompass basic investigations into dexmedetomidine, including stress response and neuroinflammation, as well as clinical studies focusing on delirium, opioid-free anesthesia, peripheral nerve block, and associated complications.

GLP-1R mediates idebenone-reduced blood glucose in mice.

GLP-1 receptor agonists (GLP-1RAs) are an innovative class of drugs with significant therapeutic value for type 2 diabetes mellitus (T2DM). The GLP-1RAs currently available on the market are biologic macromolecular peptide agents that are expensive to treat and not easy to take orally. Therefore, the development of small molecule GLP-1RAs is becoming one of the most sought-after research targets for hypoglycemic drugs. In this study, we sought to find a potential oral small molecule GLP-1RA and to evaluate its effect on insulin secretion in rat pancreatic ß cells and on blood glucose in mice. We downloaded the mRNA expression profiles of GSE102194 and GSE37936 from the Gene Expression Omnibus database. Subsequently, the small molecule compound idebenone was screened through the connectivity map database. The results of molecular docking, biolayer interferometry, and cellular thermal shift assay indicated that idebenone could bind potently with GLP-1R. Furthermore, ibebenone elevated intracellular cAMP levels. The radioimmunoassay data showed that idebenone enhanced glucose-stimulated insulin secretion via agonism of GLP-1R. Moreover, the results of oral glucose tolerance tests in C57BL/6, Glp-1r-/-, and hGlp-1r mice demonstrated that the glucose-lowering effects of idebenone were mediated by GLP-1R and that there were no species differences in the agonistic effect of idebenone on GLP-1R. In summary, idebenone reduces blood glucose in mice by promoting insulin release through agonism of GLP-1R, suggesting that idebenone is probably a potential GLP-1RA, which is expected to provide a new therapeutic strategy for the prevention and treatment of metabolic diseases such as T2DM.

Idiopathic ventricular arrhythmia originating from the vicinity of lateral tricuspid annulus: the precise origin and anatomical concerns.

BACKGROUND: Although the electrcardiographic and electrophysiological properties of ventricular arrhythmias (VA) from the vicinity of lateral tricuspid annulus (TA) have been reported in previous studies, their precise site of origin have not been addressed. OBJECTIVE: To describe the precise origin of lateral TA-VA and the relevant anatomy. METHODS: Consecutive patients with idiopathic lateral TA-VAs were reviewed and analyzed. Three-dimensional mapping system combined with intracardiac echocardiography (ICE) was used for anatomical reconstruction, mapping, and ablation. RESULTS: During the study period, 63 patients with lateral TA-VAs were included. Under ICE view, a prominent enfoldment structure was observed under the valve along lateral TA. The muscular bundle was documented in all patients (100%) within the sub-valvular enfoldment with an average number and diameter of 4±2 and 4.10±0.73mm, respectively. Initial ablation was attempted via the antegrade approach in 15 patients but succeeded in none. To reach the ventricular side of TA, the catheter needed to enter ventricular chamber and retroflexed toward the atrial side with a reverse curve. The earliest activation site was found at the valvular end of muscular bundles in 51 of the 63 (80.9%) patients with a local activation time of -26.78±4.63ms. The VAs were eliminated after an average of 4±2 seconds of ablations. CONCLUSION: The ventricular adjacent to the lateral TA exhibits a sub-valvular enfoldment-like structure, which is rich in muscular bundles and serves as the origin of TA-VAs in most patients. To reach the origins, a reverse technique is required.

Cardiac Arrhythmia Risk after Anti-Cancer Drug Exposure and Related Disease Molecular Imaging Outlook: A Systematic Review, Meta-Analysis, and Network Meta-Analysis.

BACKGROUND: Chemotherapy is the main first-line treatment, but there is a problem of adverse reactions to systemic drugs. Chemotherapeutic agents may cause adverse effects on the body, influencing the prognosis. Whether the clinical application of anthracyclines is associated with an increased arrhythmic risk remains controversial. To evaluate the arrhythmic risk of anthracyclines as a class, and the comparative risk for each drug, we conducted a systematic review, meta-analysis, and network meta-analysis. METHODS: PubMed, Web of Science, EMBASE, and the Cochrane Library were searched, up to March 2022, for randomized controlled trials, cohort studies, and case-control studies that investigated the association between anthracyclines treatment and the risk of arrhythmia. We followed the PRISMA 2020 guidelines for data selection and extraction. Outcomes were pooled using fixed effects models in cohort studies and randomized controlled studies, and random models in single-arm studies. Direct and indirect comparisons in network meta-analysis were performed using frequentist methods. RESULTS: In total, 4 cohort studies, 8 RCTs, and 18 single-arm studies were included in our analysis. Anthracyclines' use was associated with a statistically significant 90% increase in the risk of arrhythmia (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.62-2.24) and a 114% increase in the risk of supraventricular arrhythmia (OR 2.14; 95% CI 1.18-3.89). And the single-arm studies also indicated that the incidence of arrhythmia rate is 20% and the 95% CI is 15/100-25/100. Epirubicin ranked most likely to have the highest risk of arrhythmia compared with non-anthracycline antineoplastic drugs in the analysis (OR 43.07 [95% CI 2.80-2105.83]) by network meta-analysis. CONCLUSIONS: Our findings show a significant association between anthracyclines' use and an increased risk of arrhythmia, especially supraventricular arrhythmia. Epirubicin ranked with the highest probability of arrhythmia. These results indicated that cardiac rhythm should be strictly monitored during the application of anthracyclines in clinical practice, and a possible therapy for anthracycline-associated arrhythmia should be explored. Molecular imaging technology is an important means to study the mechanism of drug action on cardiac electrophysiology in the future. By imaging molecular targets in cardiac cells, the effects of drugs on the electrophysiological properties of cardiac cells can be understood, which provides information for the development of safer and more effective drugs.