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The growth in municipal solid waste incineration (MSWI) has resulted in a substantial rise in the production of fly ash in China. It is anticipated that during the "14th Five-Year Plan", the accumulated amount of fly ash stocked and disposed of at landfills will surpass 100 million tons. With the development of the economy and the implementation of garbage classification relevant policies, the pollution characteristics of heavy metal change in spatiotemporal distribution. Solidification/stabilization (S/S) pre-treatment coupled with landfill disposal is the mainstream method for fly ash. This study provides a systematic overview and comparison of the current application status and research on the mechanism of S/S technology, and the long-term stability of solidified/stabilized fly ash is a crucial factor in controlling the risks of landfills. Subsequently, it examines the influencing factors and mechanisms associated with heavy metals leaching under different environmental scenarios (meteorological factors, leachate and acid rain erosion, and carbonation, etc.), and concludes that single stabilization technology is difficult to meet long-term landfill requirements. Finally, the limits of heavy metal leaching toxicity evaluation methods and landfilled fly ash supervision were discussed, and relevant suggestions for future development were proposed. This study can provide theoretical instruction and technical support for the risk control of potential environmental risks of heavy metals in solidified/stabilized fly ash from landfills in China.
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It is imperative to unravel the dynamic variation of volatile components of vine tea during processing to provide guidance for tea quality evaluation. In this study, the dynamic changes of volatile compounds of vine tea during processing were characterized by GC-IMS and HS-SPME/GC-MS. As a result, 103 volatile compounds were characterized by the two technologies with three overlapped ones. The random forest approach was employed to develop the models and explore key volatile compounds. 23 key compounds were explored, among which 13 were derived from GC-IMS and ten were from HS-SPME/GC-MS. Moreover, the area under the receiver operating characteristics curve with 100 cross validations by the pair-wised models were all 1 for the established models. Furthermore, the primary aroma formation mechanism for the key volatile compounds were mainly involved in fatty acid and amino acid metabolism. Besides, this study provides a theoretical support for directed processing and quality control of vine tea.
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Neuroendocrine tumors (NETs) of the pancreas are rare neoplasms that present complex challenges to diagnosis and treatment due to their indolent course. The incidence of pancreatic neuroendocrine tumors has increased significantly over the past two decades. A limited number of pancreatic neuroendocrine cell lines are currently available for the research. Here, we present 3D-iNET ORION, a novel 3-dimensional (spheroid) cell line, isolated from human pancreatic neuroendocrine tumor liver metastasis. Three-dimensionally grown (3D) cancer cell lines have gained interest over the past years as 3D cancer cell lines better recapitulate the in vivo structure of tumors, and are more suitable for in vitro and in vivo experiments. 3D-iNET ORION cancer cell line showed high potential to form tumorspheres when embedded in Matrigel matrix and expresses synaptophysin and EpCAM. Electron microscopy analysis of cancer cell line proved the presence of dense neurosecretory granules. When xenografted into athymic mice, 3D-iNET ORION cells produce slow-growing tumors, positive for chromogranin and synaptophysin. Human Core Exome Panel Analysis has shown that 3DiNET ORION cell line retains the genetic aberration profile detected in the original tumor. In conclusion, our newly developed neuroendocrine cancer cell line can be considered as a new research tool for in vitro and in vivo experiments.
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Ratones Desnudos , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patología , Tumores Neuroendocrinos/patología , Animales , Línea Celular Tumoral , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Esferoides Celulares/patología , Técnicas de Cultivo Tridimensional de Células/métodos , Modelos Biológicos , Ratones , Técnicas de Cultivo de Célula/métodosRESUMEN
Male patients who undergo prepubertal chemotherapy face the dual problems of fertility preservation in adulthood, including low testosterone, hypersexual function, and infertility. Humanin, as a small polypeptide coded within the mitochondrial DNA, with the mitochondrial short open reading frame named MOTS-c, both was believed to regulate mitochondrial homeostasis, be anti-inflammatory, improve metabolism, anti-apoptosis, and multiple pharmacological effects. However, there exists little evidence that reported Humanin and MOTS-c 's effects on moderating male spermatogenic function of patients after prepubertal chemotherapy. Here, we found that in vivo, mitochondrial polypeptides Humanin analog (HNG) and MOTS-c efficaciously protected the testicular spermatogenic function from reproductive injury. Moreover, transcriptomic sequencing analysis was performed to verify the differentially expressed genes such as Piwil2, AGT (angiotensinogen), and PTGDS (glycoprotein prostaglandin D2 synthase), which are related to the regulation of male reproductive function of male mice induced by prepubertal chemotherapy. Collectively, our data revealed that both Humanin analogs HNG and MOTS-c are the feasible approaches attached to the protective effect on the male reproductive function damaged by prepubertal chemotherapy.
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BACKGROUND: Norovirus is the predominant pathogen causing foodborne illnesses and acute gastroenteritis (AGE) outbreaks worldwide, imposing a significant disease burden. This study aimed to investigate the epidemiological characteristics and genotypic diversity of norovirus outbreaks in Hongshan District, Wuhan City. METHODS: A total of 463 AGE cases from 39 AGE-related outbreaks in Hongshan District between January 1, 2021, and June 30, 2023, were included in the study. Reverse transcription-polymerase chain reaction (RT-PCR) was used to identify norovirus types GI and GII in anal swab samples from all cases. Norovirus-positive samples were sequenced and analyzed for the open reading frame (ORF) 1/ORF2 hinge region. RESULTS: 26 norovirus infectious outbreaks were reported among 39 acute diarrheal outbreaks, including 14 outbreaks in kindergartens, 8 in elementary schools, and 4 in universities. Based on clinical symptoms and epidemiological investigations, a total of 1295 individuals were identified as having been exposed to norovirus, yielding an attack rate of 35.75 %. A higher proportion of outbreaks was observed during the winter and spring seasons (38.46 %). Additionally, norovirus-positive samples were subjected to sequencing and analysis of the open reading frame (ORF) 1/ORF2 hinge region. Genotypic data for norovirus was successfully obtained from 18 (69.23 %) of the infectious outbreaks, revealing 10 distinct recombinant genotypes. GII.4 Sydney 2012 [P31] and GII.17[P17] were the predominant strains in 2021 and 2022, GII.3 [P12] emerged as the dominant strain in 2023. CONCLUSION: Norovirus outbreaks in Hongshan District predominantly occurred in crowded educational institutions, with peaks in the cold season and a high attack rate in universities. GII.3 [P12] has become the locally predominant strain.
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Infecciones por Caliciviridae , Brotes de Enfermedades , Gastroenteritis , Variación Genética , Genotipo , Norovirus , Humanos , Norovirus/genética , Norovirus/clasificación , Norovirus/aislamiento & purificación , Gastroenteritis/virología , Gastroenteritis/epidemiología , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/virología , China/epidemiología , Niño , Masculino , Femenino , Preescolar , Adolescente , Adulto , Adulto Joven , Filogenia , Lactante , Estaciones del Año , Persona de Mediana Edad , EpidemiasRESUMEN
PURPOSE: Nuclear receptor subfamily 2 group E member 1 (Nr2e1) has been regarded as an essential regulator in neural stem cells. However, its function is still not clear in hepatocytes. This study aimed to clarify the effects of Nr2e1-deficiency in hepatocytes in lipotoxic conditions. MATERIALS/METHODS: Nr2e1-knockdown AML12 âcells were generated by lentiviral vector transfection. The influences of Nr2e1-deficiency on hepatocyte survival were determined by cell cycle progression and cell apoptosis rate using flow cytometry. Real-time quantitative PCR and Western blot were used to examine the genes and protein expression related to apoptosis, lipid metabolism, and oxidative stress. Meanwhile, RNA sequencing was adopted in liver samples from Nr2e1-knockout (Nr2e1-KO) mice. RESULTS: Nr2e1 expression was observed with a significant decrease in AML12 âcells after palmitic acid-stimulation. Knockdown of Nr2e1 in AML12 âcells resulted in increased sensitivity to lipotoxicity, evidenced by a partial G0/G1 cell-cycle arrest and higher rates of cell apoptosis. Moreover, Nr2e1-knockdown AML12 âcells presented increased gene expressions relative to lipid synthesis but decreased levels of ß-oxidation related genes. Lack of Nr2e1 augmented palmitate-induced oxidative stress in hepatocytes. In vivo, differential genes in Nr2e1-KO mice liver were enriched in pathways associated with liver regeneration and cell proliferation. CONCLUSIONS: This study indicated that hepatocytes lacking Nr2e1 were more susceptible to lipotoxic-mediated damage. Nr2e1 may serve as a potential target for the development of novel therapies for lipotoxicity-induced liver injury.
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Yang-deficiency constitution (YADC) is linked to a higher vulnerability to various diseases, such as cold coagulation and blood stasis (CCBS) syndrome and infertility. Endometrial hyperplastic processes (EHPs) are a leading cause of infertility in women and are characterized by CCBS. However, it remains unclear whether YADC is related to the development of EHPs. METHODS: We recruited 202 EHPs patients including 147 with YADC (YEH group) and 55 with non-YADC (NYEH group). Fecal samples were collected from 8 YEH patients and 3 NYEH patients and analyzed using 16S rRNA V3-V4 sequencing for gut microbiota analysis. We obtained constitution survey data and a differential gut microbiota dataset from the literature for further analysis. Bioinformatics analysis was conducted using gut microbiota-related genes from public databases. RESULTS: YADC was significantly more prevalent in EHPs than non-YADC (P < 0.001), suggesting it as a potential risk factor for EHPs occurrence (ORpopulation survey = 13.471; ORhealthy women = 5.173). The YEH group had higher levels of inflammation, estrogen, and tamoxifen-related flora compared to NYEH and healthy YADC groups. There was an interaction between inflammation, estrogen, differential flora, and EHPs-related genes, particularly the TNF gene (related to inflammation) and the EGFR gene (related to estrogen), which may play a crucial role in EHPs development. CONCLUSION: YEH individuals exhibit significant changes in their gut microbiota compared to NYEH and healthy YADC. The interaction between specific microbiota and host genes is believed to play a critical role in the progression of EHPs.
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Nucleosomes play a crucial role in regulating gene expression through their composition and post-translational modifications. When cells die, intracellular endonucleases are activated and cleave chromatin into oligo- and mono-nucleosomes, which are then released into the body fluids. Studies have shown that the levels of nucleosomes are increased in serum and plasma in various cancer types, suggesting that analysis of circulating nucleosomes can provide an initial assessment of carcinogenesis. However, it should be noted that elevated serum nucleosome levels may not accurately diagnose certain tumor types, as increased cell death may occur in different pathological conditions. Nevertheless, detection of circulating nucleosomes and their histone modifications, along with specific tumor markers, can help diagnose certain types of cancer. Furthermore, monitoring changes in circulating nucleosome levels during chemotherapy or radiotherapy in patients with malignancies can provide valuable insights into clinical outcomes and therapeutic efficacy. The utilization of circulating nucleosomes as biomarkers is an exciting and emerging area of research, with the potential for early detection of various diseases and monitoring of treatment response. Integrating nucleosome-based biomarkers with existing ones may improve the specificity and sensitivity of current assays, offering the possibility of personalized precision medical treatment for patients.
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Neoplasias , Nucleosomas , Humanos , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Biomarcadores de Tumor , CromatinaRESUMEN
BACKGROUND: Some studies have suggested that hepatitis B virus (HBV) infection had a negative association with semen quality, but the conclusions have been inconsistent. The purpose of our study was to systematically assess the association between HBV infection and semen parameters. METHODS: We searched electronic databases for studies published from January 1980 to August 2023. Eleven studies were included in the analysis. Primary outcomes were semen volume, sperm concentration, sperm morphology, sperm motility and sperm progressive motility. We also conducted a subgroup analysis between China and other countries. RESULT: Compared with the semen quality of HBV-negative men, HBV infection had a negative association with semen volume (MD: -0.20 mL, 95%CI: -0.32 to - 0.09, P = 0.0004), sperm concentration (MD: -4.46 × 106/mL, 95%CI: -7.09 to - 1.84, P = 0.0009), sperm morphology (MD: -2.49%, 95%CI: -4.35 to - 0.64, P = 0.008), sperm motility (MD: -6.85%, 95%CI: -11.53 to - 2.18, P = 0.004), and sperm progressive motility (MD: -6.63%, 95%CI: -10.24 to - 3.02, P = 0.0003). However, HBV infection had no significant association with total sperm count (MD: -31.50 × 106, 95%CI: -74.11 to 11.10, P = 0.15). The association between HBV and semen quality were inconsistent between the subgroups. CONCLUSION: HBV infection had a negative association with sperm concentration, motility, morphology, and semen volume. However, The association between HBV and total sperm count remain unclear. This metaanalysis suggests that we should pay attention to the adverse effect of HBV on sperm quality, and several studies have reported the relevant mechanisms. But due to the significant heterogeneity among studies on some semen parameters, further large and well-designed researches are needed before introducing clinical management recommendations.
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Hepatitis B , Análisis de Semen , Humanos , Masculino , Virus de la Hepatitis B , Motilidad EspermáticaRESUMEN
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) restricts platelet activation via platelet collagen receptor GPVI/FcRγ-chain. In this study, screening against collagen-induced platelet aggregation was performed to identify functional CEACAM1 extracellular domain fragments. CEACAM1 fragments, including Ala-substituted peptides, were synthesized. Platelet assays were conducted on healthy donor samples for aggregation, cytotoxicity, adhesion, spreading, and secretion. Mice were used for tail bleeding and FeCl3-induced thrombosis experiments. Clot retraction was assessed using platelet-rich plasma. Extracellular segments of CEACAM1 and A1 domain-derived peptide QDTT were identified, while N, A2, and B domains showed no involvement. QDTT inhibited platelet aggregation. Ala substitution for essential amino acids (Asp139, Thr141, Tyr142, Trp144, and Trp145) in the QDTT sequence abrogated collagen-induced aggregation inhibition. QDTT also suppressed platelet secretion and "inside-out" GP IIb/IIIa activation by convulxin, along with inhibiting PI3K/Akt pathways. QDTT curtailed FeCl3-induced mesenteric thrombosis without significantly prolonging bleeding time, implying the potential of CEACAM1 A1 domain against platelet activation without raising bleeding risk, thus paving the way for novel antiplatelet drugs.
What is the context? The study focuses on Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and its role in platelet activation, particularly through the GPVI/FcRγ-chain pathway.The research aims to identify specific fragments of CEACAM1's extracellular domain that could restrict platelet activation, without increasing bleeding risk.What is new? The researchers identified a peptide called QDTT derived from the A1 domain of CEACAM1's extracellular segment. This peptide demonstrated the ability to inhibit platelet aggregation, secretion, and GP IIb/IIIa activation.The study also revealed that specific amino acids within the QDTT sequence were essential for its inhibitory effects on collagen-induced aggregation.What is the impact? The findings suggest that the A1 domain-derived peptide QDTT from CEACAM1 could serve as a potential basis for developing novel antiplatelet drugs. This peptide effectively limits platelet activation and aggregation without significantly prolonging bleeding time, indicating a promising approach to managing thrombosis and related disorders while minimizing bleeding risks.
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Proteína CEACAM1 , Cloruros , Compuestos Férricos , Trombosis , Ratones , Animales , Glicoproteínas de Membrana Plaquetaria/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Agregación Plaquetaria , Plaquetas/metabolismo , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/metabolismo , Péptidos/farmacología , Colágeno/farmacología , Trombosis/metabolismoRESUMEN
Cardiac Vascular disease particularly myocardial infarction (MI) is a threat to health worldwide. microRNAs (miRNAs) have been shown to regulate myocardial fibrosis. Therefore, it is potential to investigate the mechanism of miRNA and fibrosis following myocardial infarction. Hypoxia human cardiac microvascular endothelial cells (HCMECs) were selected for the vitro experimental model. The miR-146a-5p expression was tested via RT-qPCR. The level of endothelial-to-mesenchymal transition (EndMT) and fibrosis markers were detected by Western blotting and immunofluorescence. Then, the inflammation, cell viability and apoptosis were investigated. The target was predicted by an online database and verified by a dual-luciferase activity assay. An MI mouse model was created to validate that miR-146a-5p regulates cardiac fibrosis in vivo. MI mouse was transfected with miR-146a-5p lentivirus. Subsequently, its effect on cardiac fibrosis of infarcted hearts was assessed by In situ hybridization (ISH), Immunohistochemistry (IHC), Triphenylterazolium chloride (TTC) staining and Masson staining. Herein, we confirmed that miR-146a-5p was down-regulated in hypoxia HCMECs. Overexpression of miR-146a-5p inhibited hypoxia-induced cardiac fibrosis following myocardial infarction by inhibiting EndMT in HCMECs. Thioredoxin-interacting protein (TXNIP) was a target that was negatively regulated by miR-146a-5p. Up-regulation of miR-146a-5p inhibited cardiac fibrosis via regulating EndMT by targeting TXNIP, and it also regulated EndMT to inhibit cardiac fibrosis in vivo.
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Cardiomiopatías , MicroARNs , Infarto del Miocardio , Animales , Humanos , Ratones , Apoptosis , Cardiomiopatías/metabolismo , Células Endoteliales , Transición Endotelial-Mesenquimatosa , Fibrosis , Hipoxia/complicaciones , Hipoxia/genética , MicroARNs/genética , MicroARNs/metabolismo , Infarto del Miocardio/genética , Infarto del Miocardio/prevención & control , Infarto del Miocardio/metabolismoRESUMEN
We aimed to evaluate the reliable rate of normal/balanced embryos for reciprocal translocation and Robertsonian translocation carriers and to provide convincing evidence for clinical staff to conduct genetic counselling regarding common structural rearrangements to alleviate patient anxiety. The characteristics of 39,459 embryos that were sourced from unpublished data and literature were analyzed. The samples consisted of 17,536 embryo karyotypes that were not published and 21,923 embryo karyotypes obtained from the literature. Using the PubMed, Cochrane Library, Web of Science, and Embase databases, specific keywords were used to screen the literature for reciprocal translocation and Robertsonian translocation. The ratio of normal/balanced embryos in the overall data was calculated and analyzed, and we grouped the results according to gender to confirm if there were gender differences. We also divided the data into the cleavage stage and blastocyst stage according to the biopsy period to verify if there was a difference in the ratio of normal/balanced embryos. By combining the unpublished data and data derived from the literature, the average rates of normal/balanced embryos for reciprocal translocation and Robertsonian translocation carriers were observed to be 26.96% (7953/29,495) and 41.59% (4144/9964), respectively. Reciprocal translocation and Robertson translocation exhibited higher rates in male carriers than they did in female carriers (49.60% vs. 37.44%; 29.84% vs. 27.67%). Additionally, the data for both translocations exhibited differences in the normal/balanced embryo ratios between the cleavage and blastocyst stages of carriers for both Robertsonian translocation and reciprocal translocation (36.07% vs 43.43%; 24.88% vs 27.67%). The differences between the two location types were statistically significant (P < 0.05). The normal/balanced ratio of embryos in carriers of reciprocal and RobT was higher than the theoretical ratio, and the values ranged from 26.96% to 41.59%. Moreover, the male carriers possessed a higher number of embryos that were normal or balanced. The ratio of normal/balanced embryos in the blastocyst stage was higher than that in the cleavage stage. The results of this study provide a reliable suggestion for future clinic genetic consulting regarding the rate of normal/balanced embryos of reciprocal translocation and Robertsonian translocation carriers.
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Fertilización In Vitro , Diagnóstico Preimplantación , Embarazo , Humanos , Masculino , Femenino , Índice de Embarazo , Diagnóstico Preimplantación/métodos , Translocación Genética , BlastocistoRESUMEN
To explore the influences of chemical oxidation on the physiological and ecological functions of indigenous microorganisms during contaminated soil remediation, three oxidants, including KMnO4, Na2S2O8, and O3, were selected to investigate their remediation effects on PAHs and the responses to indigenous microorganisms under different liquid-solid ratios, in this study. The results showed that:when the ΣPAHs concentration was 679.1 mg·kg-1 and the dosage of KMnO4 and Na2S2O8 was 1%, the removal efficiency of ΣPAHs reached up to 96.9% and 95.7% under the liquid-solid ratio of 6:1; for the O3 treatment, the removal efficiency of ΣPAHs was the highest(82.3%) at the O3 dosage and the liquid-solid ratio of 72 mg·min-1 and 8:1, respectively. The removal efficiency of low ring(3-4 rings) PAHs was higher than that of high ring(5-6 rings) PAHs under different liquid-solid ratios. The highest removal efficiencies were observed for phenanthrene and acenaphthene, whereas for benzo[a]pyrene, only the KMnO4treatment provided an effective performance, showing the highest removal efficiency of 97.4%. The microbial quantity analysis indicated that the quantity of soil microorganisms in the soil dropped sharply after being treated with KMnO4, decreasing from 108 copies·g-1 to 105 copies·g-1, whereas it changed only slightly after being treated with Na2S2O8 and O3. The community structure analysis showed that Proteobacteria were predominant in the contaminated soil, with the relative abundance of 99.5%. The addition of KMnO4 and Na2S2O8 significantly increased the microbial diversity; in particular, the relative abundance of a variety of microorganisms(such as Ralstonia and Acinetobacter) that can degrade PAHs was remarkably increased. The analysis of microbial metabolic function pathways revealed that chemical oxidation could simultaneously increase the relative abundance of PAHs-degrading bacteria and improve the ability of organic metabolism. Overall, the KMnO4 treatment greatly altered the quantity of microorganisms and the structure of the microbial community and the relative abundance of PAHs-degrading microorganisms at the liquid-solid ratio of 6:1.
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Coque , Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , Oxidantes/química , Hidrocarburos Policíclicos Aromáticos/análisis , Coque/análisis , Contaminantes del Suelo/análisis , Biodegradación Ambiental , Suelo/química , Microbiología del SueloRESUMEN
Background: Despite continuous advances in microsurgical and endovascular techniques, the treatment of complex aneurysms remains challenging. Aneurysms that are dilemmatic for conventional clipping or endovascular coiling often require bypass as part of a strategy to reduce the risk of ischemic complications. In anatomically favorable sites, the intracranial-intracranial in situ bypass may be an appealing choice. This article details the surgical strategies, operative nuances, and clinical outcomes of this technique with a consecutive series in our department. Methods: A retrospective review of a prospectively maintained neurosurgical patient database was performed to identify all patients treated with side-to-side in situ bypass from January 2016 to June 2022. In total, 12 consecutive patients, including 12 aneurysms, were identified and included in the series. The medical records, surgical videos, neuroimaging studies, and follow-up clinic notes were reviewed for every patient. Results: Of the 12 aneurysms, there were 5 middle cerebral artery aneurysms, 4 anterior cerebral artery aneurysms, and 3 posterior inferior cerebellar artery aneurysms. The morphology of the aneurysms was fusiform in 8 patients and saccular in the remaining 4 patients. There were 3 patients presented with subarachnoid hemorrhage. The treatment modality was simple in situ bypass in 8 cases and in situ bypass combined with other modalities in 4 cases. Bypass patency was confirmed in all cases by intraoperative micro-doppler probe and (or) infrared indocyanine green (ICG) video angiography intraoperatively and with digital subtraction angiography (DSA) or computed tomography angiography (CTA) postoperatively. None of the patients developed a clinically manifested stroke due to the procedure though a callosomarginal artery was intentionally removed in one patient. The median follow-up period was 16.2 months (6-36). All patients had achieved improved or unchanged modified Rankin scale scores at the final follow-ups. Conclusion: Cerebral revascularization technique remains an essential skill for the treatment of complex aneurysms. The in situ bypass is one of the most effective techniques to revascularize efferent territory when vital artery sacrifice or occlusion is unavoidable. The configuration of in situ bypass should be carefully tailored to each case, with consideration of variations in anatomy and pathology of the complex aneurysms.
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Protein phosphatase 2A (PP2A) is one of the most common serine/threonine phosphatases in mammalian cells, and it primarily functions to regulate cell signaling, glycolipid metabolism and apoptosis. The catalytic subunit of PP2A (PP2Ac) plays an important role in the functions of the protein. However, there are few reports on the regulatory role of PP2Ac in pancreatic ß-cells under lipotoxic conditions. In the present study, mouse insulinoma 6 (MIN6) pancreatic cells were transfected with short hairpin RNAs to generate PP2Ac knockdown cells and incubated with palmitate (PA) to establish a lipotoxicity model. Serine/threonine phosphatase assay system, Cell Counting Kit-8, flow cytometry, enzyme-linked immunosorbent assay and western blotting were used to measure PP2A activity, cell viability, apoptosis, oxidative stress and insulin secretion in the cells. In addition, a mouse model of lipotoxicity was established with a high-fat diet (HFD) and the knockdown of PP2Ac using adeno-associated viruses to interfere with PP2Ac expression in the pancreatic tissues. The activity of PP2A in the mouse pancreatic tissue and the serum insulin level were measured. Furthermore, the proliferation of mouse pancreatic ß-cells was assessed using pancreatic tissue immunofluorescence. PP2Ac knockdown inhibited lipotoxicity-induced PP2A hyperactivation, increased the resistance of pancreatic ß-cells to lipotoxicity and attenuated PA-induced apoptosis in MIN6 cells. It also protected the endoplasmic reticulum and mitochondria, and ameliorated insulin secretion. The results of mRNA sequencing and western blotting analysis suggested that the protective effects of PP2Ac knockdown in MIN6 cells may be mediated via the MAPK pathway. Moreover, the results of the animal experiments suggested that specific knockdown of pancreatic PP2Ac effectively attenuated HFD-induced insulin resistance and reduced the compensatory proliferation of pancreatic ß-cells in mice. In summary, the present study revealed the effects of interfering with PP2Ac gene expression on pancreatic ß-cells in vivo and in vitro and the underlying mechanisms, which may provide insights for the treatment of type 2 diabetes mellitus in the clinic.
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The waste sector is a significant source of greenhouse gas(GHG) emissions and clarifying its emission trends and characteristics is the premise for formulating GHG emission reduction strategies. Using the IPCC inventory model, the GHG emissions from the municipal solid waste(MSW) sector in China during 2010 to 2020 were estimated. The results showed that GHG emissions increased from 42.5 Mt in 2010 to 75.3 Mt in 2019, then decreased to 72.1 Mt in 2020. MSW landfills were the main source of GHG emissions. Further, with the increase in the proportion of waste incineration, the proportion of GHG incineration increased rapidly from 16.5% in 2010 to 60.1% in 2020. In terms of regional distribution, East and South China were the regions with the highest emissions, and Guangdong, Shandong, Jiangsu, and Zhejiang were the provinces with the largest GHG emissions. Implementing MSW classification, changing the MSW disposal modes from landfilling to incineration, improving the LFG collection efficiency of landfills, and using biological functional materials as the cover soil to strengthen the methane oxidation efficiency are the main measures to achieve GHG emission reduction in waste sectors.
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Introduction: Luteolin inhibits platelet activation and thrombus formation, but the mechanisms are unclear. This study investigated the effects of luteolin on GPVI-mediated platelet activation in vitro and explored the effect of luteolin on thrombosis, coagulation, and platelet production in vivo. Methods: Washed human platelets were used for aggregation, membrane protein expression, ATP, Ca2+, and LDH release, platelet adhesion/spreading, and clot retraction experiments. Washed human platelets were used to detect collagen and convulxin-induced reactive oxygen species production and endogenous antioxidant effects. C57BL/6 male mice were used for ferric chloride-induced mesenteric thrombosis, collagen-epinephrine induced acute pulmonary embolism, tail bleeding, coagulation function, and luteolin toxicity experiments. The interaction between luteolin and GPVI was analyzed using solid phase binding assay and surface plasmon resonance (SPR). Results: Luteolin inhibited collagen- and convulxin-mediated platelet aggregation, adhesion, and release. Luteolin inhibited collagen- and convulxin-induced platelet ROS production and increased platelet endogenous antioxidant capacity. Luteolin reduced convulxin-induced activation of ITAM and MAPK signaling molecules. Molecular docking simulation showed that luteolin forms hydrogen bonds with GPVI. The solid phase binding assay showed that luteolin inhibited the interaction between collagen and GPVI. Surface plasmon resonance showed that luteolin bonded GPVI. Luteolin inhibited integrin αIIbß3-mediated platelet activation. Luteolin inhibited mesenteric artery thrombosis and collagen- adrenergic-induced pulmonary thrombosis in mice. Luteolin decreased oxidative stress in vivo. Luteolin did not affect coagulation, hemostasis, or platelet production in mice. Discussion: Luteolin may be an effective and safe antiplatelet agent target for GPVI. A new mechanism (decreased oxidative stress) for the anti-platelet activity of luteolin has been identified.
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Lower limb exoskeletons and exosuits ("exos") are traditionally designed with a strong focus on mechatronics and actuation, whereas the "human side" is often disregarded or minimally modeled. Muscle biomechanics principles and skeletal muscle response to robot-delivered loads should be incorporated in design/control of exos. In this narrative review, we summarize the advances in literature with respect to the fusion of muscle biomechanics and lower limb exoskeletons. We report methods to measure muscle biomechanics directly and indirectly and summarize the studies that have incorporated muscle measures for improved design and control of intuitive lower limb exos. Finally, we delve into articles that have studied how the human-exo interaction influences muscle biomechanics during locomotion. To support neurorehabilitation and facilitate everyday use of wearable assistive technologies, we believe that future studies should investigate and predict how exoskeleton assistance strategies would structurally remodel skeletal muscle over time. Real-time mapping of the neuromechanical origin and generation of muscle force resulting in joint torques should be combined with musculoskeletal models to address time-varying parameters such as adaptation to exos and fatigue. Development of smarter predictive controllers that steer rather than assist biological components could result in a synchronized human-machine system that optimizes the biological and electromechanical performance of the combined system.
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Chemical reduction combined with microbial stabilization is a green and efficient method for the remediation of hexavalent chromium (Cr(VI)) contaminated soil. In this study, the combination of ferrous sulfate with kitchen waste digestate was applied to reduce and immobilize Cr(VI) in chromite ore processing residue (COPR) contaminated soils, and systematically evaluated the remediation performance of Cr(VI) compared with several typical reducing agents (i.e., ferrous sulfate, zero valent iron, sodium thiosulfate, ferrous sulfide, and calcium polysulfide). The results showed that the combination of ferrous sulfate and digestate had superior advantages of a lower dosage of reducing agent and a long-term remediation effect compared to other single chemical reductants. Under an Fe(II):Cr(VI) molar ratio of 3:1% and 4% digestate (wt), the content of Cr(VI) in the soil decreased to 5.07 mg/kg after 60 days of remediation. Meanwhile, the leaching concentrations of Cr(VI) were below detection limit, which can meet the hazardous waste toxicity leaching standard. The risk level of Cr pollution was decreased from very high risk to low risk. The X-ray photoelectron spectroscopy (XPS) results further demonstrated that the combined treatments were beneficial to Cr(VI) reduction and stabilization. The abundance of bacteria with Cr(VI) reducing ability was higher than other treatments. Moreover, the high abundance of carbon and nitrogen metabolism in the combined treatments demonstrated that the addition of digestate was beneficial to the recovery and flourishing of Cr(VI)-reducing related microorganisms in COPR contaminated soils. This work provided an alternative way on Cr(VI) remediation in COPR contaminated soils.
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With the development of incineration technologies, incineration has become the most common treatment method of municipal solid waste in China. However, stabilized fly ash may enter landfills during the transition from landfill to incineration, which caused uncertain impact on landfill waste stabilization. Two simulated co-landfill columns were constructed based on different co-landfill methods (layer co-landfill and mixed co-landfill) to investigate the effect of stabilized fly ash co-landfilled municipal solid waste for bacterial community succession and change in metabolic pathways during hydrolysis-acidogenesis stage. The mixed co-landfill method resulted in higher degree of organic matter degradation, and the concentrations of volatile fatty acids (VFA) and chemical oxygen demand (COD) in leachate were higher. The dominant phyla were Firmicutes in the layered co-landfill column and Bacteroidetes in mixed co-landfill column. The dominant genera for the total bacterial composition and VFA production were different, Pseudomonas and Propionibacterium, Proteiniphilum and unclassified Bacteroides were the dominant genera responsible for VFA generation in the layered and mixed co-landfill columns. The genes for butyrate production were enriched in the layered co-landfill column, whereas those related to acetate production were enriched in mixed co-landfill column. However, the layered co-landfill inhibited the microbial metabolic activity at the end of the co-landfill process.