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JOURNAL/nrgr/04.03/01300535-202504000-00031/figure1/v/2024-07-06T104127Z/r/image-tiff Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia. Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia. Currently, studies have reported increased oscillation power in cases of levodopa-induced dyskinesia. However, little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia. Furthermore, the role of the dopamine D3 receptor, which is implicated in levodopa-induced dyskinesia, in movement disorder-related changes in neural oscillations is unclear. We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson's disease. Furthermore, levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components, as well as bidirectional primary motor cortex (M1) ↔ dorsolateral striatum gamma flow. Administration of PD128907 (a selective dopamine D3 receptor agonist) induced dyskinesia and excessive gamma oscillations with a bidirectional M1 ↔ dorsolateral striatum flow. However, administration of PG01037 (a selective dopamine D3 receptor antagonist) attenuated dyskinesia, suppressed gamma oscillations and cortical gamma aperiodic components, and decreased gamma causality in the M1 → dorsolateral striatum direction. These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity, and that it has potential as a therapeutic target for levodopa-induced dyskinesia.

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Polybromodiphenyl ethers (PBDEs), the widely used flame retardants, are common contaminants in surface soils at e-waste recycling sites. The association of PBDEs with soil colloids has been observed, indicating the potential risk to groundwater due to colloid-facilitated transport. However, the extent to which soil colloids may enhance the spreading of PBDEs in groundwater is largely unknown. Herein, we report the co-transport of decabromodiphenyl ester (BDE-209) and soil colloids in saturated porous media. The colloids released from a soil sample collected at an e-waste recycling site in Tianjin, China, contain high concentration of PBDEs, with BDE-209 being the most abundant conger (320 ± 30 mg/kg). The colloids exhibit relatively high mobility in saturated sand columns, under conditions commonly observed in groundwater environments. Notably, under all the tested conditions (i.e., varying flow velocity, pH, ionic species and ionic strength), the mass of eluted BDE-209 correlates linearly with that of eluted soil colloids, even though the mobility of the colloids varies markedly depending on the specific hydrodynamic and solution chemistry conditions involved. Additionally, the mass of BDE-209 retained in the columns also correlates strongly with the mass of retained colloids. Apparently, the PBDEs remain bound to soil colloids during transport in porous media. Findings in this study indicate that soil colloids may significantly promote the transport of PBDEs in groundwater by serving as an effective carrier. This might be the reason why the highly insoluble and adsorptive PBDEs are found in groundwater at some PBDE-contaminated sites.

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Metastasis is the leading cause of mortality in patients with malignant tumors, particularly characterized by peritoneal metastases originating from gastric, ovarian, and colorectal cancers. Regarded as the terminal phase of tumor progression, peritoneal metastasis presents limited therapeutic avenues and is associated with a dismal prognosis for patients. The epithelial-mesenchymal transition (EMT) is a crucial phenomenon in which epithelial cells undergo significant changes in both morphology and functionality, transitioning to a mesenchymal-like phenotype. This transition plays a pivotal role in facilitating tumor metastasis, with transcription factors being key mediators of EMT's effects. Consequently, we provide a retrospective summary of the efforts to identify specific targets among EMT-related transcription factors, aimed at modulating the onset and progression of peritoneal metastatic cancer. This summary offers vital theoretical underpinnings for developing treatment strategies against peritoneal metastasis.

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OBJECTIVES: The purpose of this study was to investigate the clinical effect of treating axillary osmidrosis by trimming the apocrine glands under direct vision after blunt dissection of the axillary flap through double mini-incisions on both sides of the axilla to prevent postoperative hematoma. METHODS: The clinical data of 108 patients with axillary osmidrosis were retrospectively analyzed. Treatment involved blunt dissection of the axillary flap through double mini-incisions and trimming of the apocrine glands under direct vision. The surgical duration, hematoma incidence, flap necrosis rate, incision healing rate, incision VSS score, comfort level, axillary odor cure rate, and satisfaction rating were all statistically analyzed. RESULTS: The average surgical duration was 72.45±5.71 min. The cure rate of axillary osmidrosis was 100%. Postoperative complications, including delayed incision healing 12 days after surgery (1 patient), a small hematoma (2 patients), and local flap necrosis (1 patient), were minor. No infection, malodor, or recurrence was observed. The VAS score for patient comfort was 8.53±0.89, the VAS score for patient satisfaction was 8.87±0.98, and the VSS score for the incision was 0.84±0.99. CONCLUSION: This retrospective study demonstrated that the trimming of apocrine glands after blunt dissection of the axillary flap through double mini-incisions on both sides of the axilla effectively controlled bleeding. This approach significantly reduces the complication rate of axillary osmidrosis surgery and ensures the complete trimming of apocrine glands, eradicating axillary odor and maintaining a good appearance.

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Membrane protein-mediated resistance is a multidisciplinary challenge that spans fields such as medicine, agriculture, and environmental science. Understanding its complexity and devising innovative strategies are crucial for treating diseases like cancer and managing resistant pests in agriculture. This paper explores the dual nature of resistance mechanisms across different organisms: On one hand, animals, bacteria, fungi, plants, and insects exhibit convergent evolution, leading to the development of similar resistance mechanisms. On the other hand, influenced by diverse environmental pressures and structural differences among organisms, they also demonstrate divergent resistance characteristics. Membrane protein-mediated resistance mechanisms are prevalent across animals, bacteria, fungi, plants, and insects, reflecting their shared survival strategies evolved through convergent evolution to address similar survival challenges. However, variations in ecological environments and biological characteristics result in differing responses to resistance. Therefore, examining these differences not only enhances our understanding of adaptive resistance mechanisms but also provides crucial theoretical support and insights for addressing drug resistance and advancing pharmaceutical development.

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Rodent-infested bald spots are crucial indicators of rodent infestation in grasslands. Leveraging Unmanned Aerial Vehicle (UAV) remote sensing technology for discerning detrimental bald spots among plateau pikas has significant implications for assessing associated ecological hazards. Based on UAV-visible light imagery, we classified and recognized the characteristics of plateau pika habitats with five supervised classification algorithms, i.e., minimum distance classification (MinD), maximum likelihood classification (ML), support vector machine classification (SVM), Mahalanobis distance classification (MD), and neural network classification (NN) . The accuracy of the five methods was evaluated using a confusion matrix. Results showed that NN and SVM exhibited superior performance than other methods in identifying and classifying features indicative of plateau pika habitats. The mapping accuracy of NN for grassland and bald spots was 98.1% and 98.5%, respectively, with corresponding user accuracy was 98.8% and 97.7%. The overall model accuracy was 98.3%, with a Kappa coefficient of 0.97, reflecting minimal misclassification and omission errors. Through practical verification, NN exhibited good stability. In conclusion, the neural network method was suitable for identifying rodent-damaged bald spots within alpine meadows.

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The structural integrity of the sperm flagellum is essential for proper sperm function. Flagellar defects can result in male infertility, yet the precise mechanisms underlying this relationship are not fully understood. CCDC181, a coiled-coil domain-containing protein, is known to localize on sperm flagella and at the basal regions of motile cilia. Despite this knowledge, the specific functions of CCDC181 in flagellum biogenesis remain unclear. In this study, Ccdc181 knockout mice were generated. The absence of CCDC181 led to defective sperm head shaping and flagellum formation. Furthermore, the Ccdc181 knockout mice exhibited extremely low sperm counts, grossly aberrant sperm morphologies, markedly diminished sperm motility, and typical multiple morphological abnormalities of the flagella (MMAF). Additionally, an interaction between CCDC181 and the MMAF-related protein LRRC46 was identified, with CCDC181 regulating the localization of LRRC46 within sperm flagella. These findings suggest that CCDC181 plays a crucial role in both manchette formation and sperm flagellum biogenesis.

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BACKGROUND: The increase in the rate of multiple pregnancies in clinical practice is associated with assisted reproductive technology (ART). Given the high risk of dichorionic triamniotic (DCTA) triplet pregnancies, reducing DCTA triplet pregnancies to twin or singleton pregnancies is often beneficial. CASE PRESENTATION: This article reports on two cases of DCTA triplet pregnancies resulting from two blastocyst transfers. Given the high risk of complications such as twin-to-twin transfusion syndrome (TTTS) in monochorionic diamniotic (MCDA) twin pregnancies, patients have a strong desire to preserve the dichorionic diamniotic (DCDA) twins. Multifetal pregnancy reduction (MFPR) was performed in both cases to continue the pregnancy with DCDA twins by reducing one of the MCDA twins. Both of the pregnant women in this report eventually gave birth to healthy twins at 37 weeks. CONCLUSIONS: For infertile couples with multiple pregnancies but with a strong desire to remain the DCDA twins, our report suggests that reducing DCTA triplets to DCDA twin pregnancies may be an option based on clinical operability and assessment of surgical difficulty.

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Objectives: To comprehensively analyze the randomized controlled clinical trials of integrated traditional Chinese medicine (TCM) and western medicine in the treatment of metabolic syndrome (MetS), and to explore the clinical efficacy and safety of different TCM combined with western medicine for MetS. The purpose of this study is to provide specific suggestions for clinical guidance in the treatment of MetS. Methods: A comprehensive literature review was conducted across several databases, including China Knowledge Network, Wanfang Data, VIP Information, China Biomedical Literature Service System, Embase, PubMed, and Web of Science, up to October 2023. The scope of this review was confined to RCTs focusing on the treatment of metabolic syndrome through an integrated approach of TCM and Western medicine. The primary efficacy endpoints analyzed were clinical efficacy, fasting blood glucose (FBG), triglyceride (TG), and high-density lipoprotein (HDL). Data synthesis and analysis were performed using Stata 16 and RevMan 5.4 for both traditional and network meta-analyses. Results: The findings from both traditional and network meta-analyses reveal that the combination of JiangZhiHuoXue pills (JZHX) + Conventional Western Medicine (CWM) significantly reduces FBG levels. Similarly, the AnShenNingXin capsules (ASNX) + CWM combination markedly lowers TG levels, while the FuFangQiMa capsules (FFQM) + CWM combination shows enhanced efficacy in elevating HDL levels. Notably, the combination of KangNing capsules (KNJN) + CWM demonstrates a more pronounced clinical effect compared to CWM/placebo alone. Conclusions: The study concludes that the synergistic combination of TCM and Western medicine exhibits superior therapeutic benefits in treating MetS compared to CWM/Placebo treatments alone. The combinations of JZHX, AXNX, FFQM, and KNJN with CWM emerge as potentially effective treatments.

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Posttransplantation complications pose a major challenge to the long-term survival and quality of life of organ transplant recipients. These complications encompass immune-mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation. Here, we provide a comprehensive overview of the clinical features, risk factors, and molecular mechanisms of major posttransplantation complications. We systematically summarize the current understanding of the immunological basis of allograft rejection and graft-versus-host disease, the metabolic dysregulation associated with immunosuppressive agents, and the role of oncogenic viruses in posttransplantation malignancies. Furthermore, we discuss potential prevention and intervention strategies based on these mechanistic insights, highlighting the importance of optimizing immunosuppressive regimens, enhancing infection prophylaxis, and implementing targeted therapies. We also emphasize the need for future research to develop individualized complication control strategies under the guidance of precision medicine, ultimately improving the prognosis and quality of life of transplant recipients.

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Vacancy engineering and heterostructure construction are regarded as potent approaches for synergistically boosting hydrogen production in renewable energy conversion. Herein, a selective phosphorization strategy was implemented to fabricate coral-like ZnO/FeCoP@N-doped carbon hierarchical microspheres (ZnO/FeCoP@NCHMS) via only controllably phosphorizing the Co and Fe atoms in a precursor, which was formed by generating ZnCoFe LDH on the surface of a zinc cobalt coordination polymer microsphere. Then, by adopting a reduction treatment for ZnO/FeCoP@NCHMS, the innovative ZnO/FeCoPv@NCHMS with abundant phosphorus vacancies (Pv) was realized. The introduction of phosphorus vacancy could optimize the electronic structures of metal phosphides and accelerate the reconstruction of active species, thus speeding up the reaction kinetic. Likewise, the plentiful heterointerfaces greatly expedite the transfer of electrons and protons, exposing ultra-high active sites. By virtue of these fascinating characters and the unique coral-like hierarchical architecture, the as-prepared ZnO/FeCoPv@NCHMS reveal preeminent electrocatalytic activities, and the overpotentials for the oxygen evolution reaction (OER) and the hydrogen evolution reaction (HER) are as low as 177 and 173 mV at 10 mA cm-2 in alkaline medium, respectively. Impressively, the water electrolysis device assembled by ZnO/FeCoPv@NCHMS requires a mere cell voltage of 1.508 V to attain a current density of 10 mA cm-2. Furthermore, the ZnO/FeCoPv@NCHMS also demonstrate extraordinary durability, sustaining operation for at least 28 h (at 100 mA cm-2) during the water splitting process. This study provides novel insights into defect regulation and heterointerface construction for overall water splitting.

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P-type organic cathode materials typically exhibit high redox potentials and fast redox kinetics, presenting broad application prospects in aqueous zinc batteries (AZBs). However, most of the reported P-type organic cathode materials exhibit limited capacity (< 100 mAh g-1), which is attributable to the low mass content ratio of oxidation-reduction active functional groups in these materials. Herein, we report a high-capacity p-type organic material, 5,12-dihydro-5,6,11,12-tetraazatetracene (DHTAT), for aqueous zinc batteries. Both experiments and calculation indicate the charge storage of DHTAT involves the adsorption/ desorption of ClO4- on the -NH- group. Benefitting from the high mass content ratio of the -NH- group in DHATA molecule, the DHATA electrode demonstrates a remarkable capacity of 224 mAh g-1 at a current density of 50 mA g-1 with a stable voltage of 1.2 V. Notably, after 5000 cycles at a high current density of 5 A g-1, DHTAT retains 73% of its initial capacity, showing a promising cycling stability. In addition, DHTAT also has good low-temperature performance and can stably cycle at -40 °C for 4000 cycles at 1 A g-1, making it a competitive candidates cathode material for low-temperature batteries.

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BACKGROUND: Selective hemihepatic vascular occlusion is utilized in both right and left hemihepatectomies to preserve blood supply to the intact lobe, maintain hemodynamic stability, and mitigate surgical risks. While this technique encompasses both intrathecal and extrathecal Glissonean pedicle transection methods, there is a lack of systematic comparative reports on these two approaches. AIM: To retrospectively analyze the clinical data of patients with hepatocellular carcinoma (HCC) undergoing laparoscopic anatomical hepatectomy in our hospital to explore the feasibility, safety, and short- and long-term efficacy of extrathecal and intrathecal Glissonean pedicle transection methods in laparoscopic left hemihepatectomy. METHODS: A retrospective study was performed to analyze the clinical data of 49 HCC patients who underwent laparoscopic left hemihepatectomy from January 2019 to December 2022 in our hospital. These patients were divided into extrathecal Glissonean pedicle transection (EGP) group (n = 24) and intrathecal Glissonean pedicle transection (IGP) group (n = 25) according to the different approaches used for selective hemihepatic vascular occlusion. The perioperative indicators, liver function indexes, complications, and follow-up findings were compared between these two groups. RESULTS: The surgeries were smooth in both groups, and no perioperative death was noted. The hepatic pedicle transection time and the operation time were (16.1 ± 2.3) minutes and (129.6 ± 19.0) minutes, respectively, in the EGP group, which were significantly shorter than those in the IGP group [(25.5 ± 2.4) minutes and (184.8 ± 26.0) minutes, respectively], both P < 0.01. There were no significant differences in intraoperative blood loss, time to anal exhaust, hospital stay, drain indwelling time, and postoperative liver function between the two groups (all P > 0.05). The incidence of postoperative complications showed no significant difference [16.67% (4/24) vs 16.0% (4/25), P > 0.05). All the 49 HCC patients were followed up after surgery (range: 11.2-53.3 months; median: 36.4 months). The overall survival rate and disease-free survival rate were not significantly different (both P > 0.05). CONCLUSION: Both extrathecal and intrathecal Glissonean pedicle approaches are effective and safe hepatic inflow occlusion techniques in laparoscopic left hemihepatectomy for HCC. However, the extrathecal approach simplifies the hepatic pedicle transection, shortens the operation time, and increases the surgical efficiency, making it a more feasible technique.

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BACKGROUND: Peutz-Jeghers syndrome (PJS) has brought significant physical, psychological and economic burdens on the patients and their families due to its early onset, diagnostic and therapeutic challenges and increased recurrence risk. AIM: To explore the current research status and emerging hotspots of PJS. METHODS: Studies on PJS published during 1994-2023 were gathered based on Web of Science Core Collection. Additionally, a case of PJS-induced intestinal intussusception, successfully treated with endoscopic methods despite three laparotomies, was highlighted. Comprehensive bibliometric and visual analysis were conducted with VOSviewer, R and CiteSpace. RESULTS: Altogether 1760 studies were identified, indicating a steady increase in the publication number. The United States had the highest influence, whereas the University of Helsinki emerged as the leading institution, and Aaltonen LA from the University of Helsinki was the most prolific author. Cancer Research, Oncogene and Endoscopy were the top three journals based on H-index. Keyword burst direction analysis revealed that "cancer risk", "management", "surveillance" and "familial pancreatic cancer" were the potential hotspots for investigation. Additionally, "early detection", "capsule endoscopy", "clinical management", "double-balloon endoscopy", "familial pancreatic cancer" and "molecular genetic basis" were identified as the key clusters of co-cited references. Endoscopic polypectomy remained effective on resolving intestinal intussusception in patients who underwent three previous laparotomies. CONCLUSION: In the last three decades, global publications related to PJS show a steadily increasing trend in number. Endoscopic management is currently a research hotspot.

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Large-scale coal mine gas explosion (CMGE) accidents have occurred occasionally and exerted a devastating effect on society. Therefore, it is essential to systematically identify the characteristics and association rules of causes of CMGE accidents through analysis on large-scale CMGE accident reports. In this study, 298 large-scale CMGE accidents in China from 2000 to 2021 were taken as the data sample, and mathematical statistical methods were adopted to analyze their general characteristics, coupling cross characteristics, and characteristics of gas accumulation and ignition sources. Moreover, the text mining technology and the Apriori algorithm were used for exploring the formation mechanism of CMGE accidents, during which 46 main causal factors were identified and 59 strong association rules were obtained. Furthermore, an accident causation network was constructed based on the co-occurrence matrix. The key causal items and sets of CMGE accidents were clarified through network centrality analysis. According to the research results, electrical equipment failure, cable short circuit, mine lamp misfire, hot-line work, and blasting spark are the key ignition sources of CMGE. Fan failure, airflow short circuit, and local ventilation fan damage are the main causes of gas accumulation. Besides, the confidence levels of two association rules of "static spark-fan failure" and "blasting spark-airflow short circuit" are higher than 70%, indicating that they are the two dominant risk-coupling paths of gas explosions. In addition, six causes appear frequently in the shortest risk paths of gas explosion and are closely related to other causes, i.e., fan failure, local ventilation fan damage, static sparks, electrical equipment failure, self-heating ignition, and friction impact sparks. This study provides a new perspective on identifying causes of accidents and their complex association mechanisms from accident report data for practical guidance in risk assessment and accident prevention.

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Non-alcoholic fatty liver disease (NAFLD) and myocardial infarction (MI) are two major health burdens with significant prevalence and mortality. This study aimed to explore the co-expressed genes to understand the relationship between NAFLD and MI and identify potential crucial biomarkers of NAFLD-related MI using bioinformatics and machine learning. Functional enrichment analysis was conducted, a co-protein-protein interaction (PPI) network diagram was constructed, and support vector machine-recursive feature elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO) techniques were employed to identify one differentially expressed gene (DEG), Thrombospondin 1 (THBS1). THBS1 demonstrated strong performance in distinguishing NAFLD patients (AUC = 0.981) and MI patients (AUC = 0.900). Immuno-infiltration analysis revealed significantly lower CD8+ T cells and higher neutrophil levels in patients with NAFLD and MI. CD8+ T cells and neutrophils were effective in distinguishing NAFLD/MI from healthy controls. Correlation analysis showed that THBS1 was positively correlated with CCR (chemokine receptor), MHC class (major histocompatibility complex class), neutrophils, parainflammation, and Tfh (follicular helper T cells), and negatively correlated with CD8+ T cells, cytolytic activity, and TIL (tumor-infiltrating lymphocytes) in NAFLD and MI patients. THBS1 emerged as a novel biomarker for diagnosing NAFLD/MI in comparison to healthy controls. The results indicate that CD8+ T cells and neutrophils could serve as inflammatory immune features for differentiating patients with NAFLD/MI from healthy individuals.

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AIMS: The purpose of this study was to analyze the dynamic trends of ischemic heart disease (IHD) mortality attributable to high low-density lipoprotein cholesterol (LDL-C). METHODS: Data on IHD mortality attributable to high LDL-C from 1990 to 2021 were extracted from the global disease burden database. Joinpoint software was used to estimate the average annual percentage change (AAPC) in the age-standardized mortality rate (ASMR). An age‒period‒cohort model was used to analyze the impacts of age, period, and cohort on these changes. The Bayesian framework was used to predict IHD mortality attributable to high LDL-C from 2022 to 2040. RESULTS: The overall ASMR of IHD attributable to high LDL-C decreased from 50. 479 per 100,000 people in 1990 to 32.286 per 100,000 people in 2021, and ASMR of IHD attributable to high LDL-C was higher in males than in females. The longitudinal age curves of the overall IHD mortality attributable to high LDL-C showed a monotonic upward trend, especially after 65 years of age. The period and cohort effect relative risk (RR) values of overall IHD mortality attributable to high LDL-C showed a downward trend. The overall ASMR of IHD attributable to high LDL-C is predicted to show a downward trend, and male IHD mortality attributable to high LDL-C is expected to be higher than that of females. CONCLUSION: This study revealed a sustained decrease in IHD mortality attributable to high LDL-C over three decades, with a continued decline expected. Despite this, gender disparities persist, with males experiencing higher mortality rates and elderly individuals remaining a vulnerable group.

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Macropsini is a tribe of Eurymelinae in the family Cicadellidae that is widely distributed worldwide. Still, its taxonomic status has been unstable, and the classification of certain clades at the genus level has been controversial. The aim of this study is to address the patterns and processes that explain the structure and the evolution of the mitogenomes of Macropsini, while contributing to the resolution of systematic issues involving five of their genera. To this task, the mitogenomes of 26 species of the tribe were sequenced and characterized, and their phylogenetic relationships were reconstructed. The results revealed that the nucleotide composition of mitochondrial genes in these 26 species was significantly skewed toward A and T. Codons ending with T or A in relative synonymous codon usage were significantly more prevalent than those ending with C or G. The parity plot, neutrality plot, and correspondence analysis revealed that mutation and selective pressure affect codon usage patterns. In the phylogenetic relationships of the Macropsini, the monophyly of Pedionis and Macropsis was well-supported. Meanwhile, Oncopsis revealed paraphyletic regarding Pediopsoides. In conclusion, this research not only contributes the valuable data to the understanding of the mitogenome of the Macropsini but also provides a reference for future investigations on codon usage patterns, potential adaptive evolution, and the phylogeny of the mitogenome within the subfamily Eurymelinae.

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ETHNOPHARMACOLOGICAL RELEVANCE: Positive evidence from clinical trials highlights the promising potential of traditional Chinese medication, Qili qiangxin capsule (QLQX), on chronic heart failure; however, limited data are available regarding its effects and mechanism in myocardial ischemia-reperfusion injury (MIRI). Herein, we aimed to explore cardioprotective effects and the underlying mechanism of QLQX in MIRI in vivo and in vitro. MATERIALS AND METHODS: Mice were subjected to left anterior descending coronary artery ligation for 30 min followed by 24 h of reperfusion with or without 7-day pretreatment with QLQX (0.234, 0.468, or 0.936 g/kg). Cardiac function, myocardial infarction, and morphological changes were evaluated. The mechanism underlying the cardio-protection of QLQX on MIRI was determined by network pharmacology based on the common genes of potential targets of QLQX and MIRI-related genes, further validated by H9c2 cardiomyocytes exposing hypoxia/reoxygenation (H/R). The viability, apoptosis, as well as autophagy and relevant signaling proteins in H9c2 were analyzed. RESULTS: QLQX pretreatment markedly improved cardiac function and decreased myocardium infarct size, apoptotic cardiomyocyte number, and LHD, CK-MB, and TnT levels in MIRI mice. QLQX could mitigate H/R-induced H9c2 cardiomyocyte injury, as evidenced by decreased cell apoptosis and LDH release and increased ATP production. QLQX effectively attenuates excessive autophagy in cardiomyocytes both in vivo and in vitro. Mechanically, network pharmacology analysis demonstrated the cardio-protection of QLQX on MIRI involving in PI3K/Akt signaling; the effects of QLQX on H/R-induced H9c2 cardiomyocytes were abolished by a specific PI3K inhibitor. CONCLUSION: QLQX protects against cardiomyocyte apoptosis and excessive autophagy via PI3K/Akt signaling during MIRI.

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INTRODUCTION: Acute lung injury (ALI) as one kind of acute pulmonary inflammatory disorder, manifests primarily as damage to alveolar epithelial cells and microvascular endothelial cells. Activation of the complement system is a common pathological mechanism in ALI induced by diverse factors, with the complement alternative pathway assuming a pivotal role. Baicalin, a flavonoid derived from the root of Scutellaria baicalensis Georgi, exhibits noteworthy biological activities. The present study attempted the interventional effects and underlying mechanisms of baicalin in microangiopathy in ALI induced by complement alternative pathway activation. METHODS: Activation of the complement alternative pathway by cobra venom factor (CVF). HMEC cells were pretreated with baicalin and then exposed to complement activation products. The expression of inflammatory mediators was detected by ELISA, and the intranuclear transcriptional activity of NF-κB was assessed by a dual fluorescent kinase reporter gene assay kit. Before establishing the ALI mouse model, baicalin or PDTC was gavaged for 7 d. CVF was injected into the tail vein to establish the ALI model. The levels of inflammatory mediators in BALF and serum were determined by ELISA. HE staining and immunohistochemistry evaluated pathological changes, complement activation product deposition, and NF-κB p65 phosphorylation in lung tissue. RESULTS: Baicalin reduced complement alternative activation product-induced expression of HMEC cells adhesion molecules (ICAM-1, VCAM-1, E-selectin) and cytokines (IL-6, TNF-α) as well as upregulation of NF-κB intranuclear transcriptional activity. Baicalin intervention reduced the number of inflammatory cells and protein content in the BALF and decreased the levels of IL-6, TNF-α, and ICAM-1 in serum and IL-6, TNF-α, ICAM-1, and P-selectin in BLAF. In addition, baicalin attenuated inflammatory cell infiltration in the lung of ALI mice and reduced the deposition of complement activation products (C5a, C5b-9) and phosphorylation of NF-κB p65 in lung tissue. CONCLUSION: Baicalin relieves complement alternative pathway activation-induced lung inflammation by inhibition of NF-κB pathway, delaying the progression of ALI.

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