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Background: Inflammation is integral to diabetes pathogenesis. The novel hematological inflammatory biomarker, platelet to white blood cell ratio (PWR), is linked with various conditions such as chronic kidney disease and stroke. However, the association of this novel clinical indicator with diabetes still remains unclear, which is investigated in this study. Materials and Methods: A total of 10,973 Chinese participants were included and grouped according to the tertiles of PWR (T1, T2, and T3 groups). Diagnosis of prediabetes and diabetes adhered to American Diabetes Association criteria. Binary logistic regression was adopted to assess the relationship between PWR and both diabetes and prediabetes. The dose-response relationship of PWR and diabetes was examined using restricted cubic spline regression. Subgroup and interaction analyses were conducted to investigate potential covariate interactions. Results: Individuals with higher PWR had better lifestyles and lipid profiles (all P < 0.05). After adjusting for all the covariates, the T2 group had a 0.83-fold (95% CI: 0.73-0.93, P < 0.01) risk of diabetes and that for the T3 group was 0.68-fold (95% CI: 0.60-0.78. P < 0.001). Dose-response analysis identified non-linear PWR-diabetes associations in the general population and females (both P < 0.05), but absent in males. Participants with prediabetes in the T2 and T3 groups had lower risks of diabetes (OR = 0.80 for the T2 group, P < 0.001 and 0.68 for the T3 group, P < 0.001) in the full models. All the sensitivity analysis support consistent conclusions. Conclusions: An increase in PWR significantly correlates with reduced diabetes risks. A non-linear PWR-diabetes relationship exists in the general population and females, but not in males. The correlation between PWR and diabetes indicates that PWR holds potentials in early identification and prevention of diabetes.
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Diabetes Mellitus , Estado Pré-Diabético , Humanos , Masculino , Feminino , China/epidemiologia , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Estado Pré-Diabético/epidemiologia , Adulto , Contagem de Leucócitos , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Plaquetas , Idoso , Contagem de Plaquetas , Leucócitos/metabolismo , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologiaRESUMO
Spinal cord injury (SCI) is a central nerve injury that often leads to loss of motor and sensory functions at or below the level of the injury. Zebrafish have a strong ability to repair after SCI, but the role of microRNAs (miRNAs) after SCI remains unclear. Locomotor behavior analysis showed that adult zebrafish recovered about 30% of their motor ability at 2 weeks and 55% at 3 weeks after SCI, reflecting their strong ability to repair SCI. Through miRNA sequencing, mRNA sequencing, RT-qPCR experiment verification, and bioinformatics predictive analysis, the key miRNAs and related genes in the repair of SCI were screened. A total of 38 miRNAs were significantly different, the top ten miRNAs were verified by RT-qPCR. The prediction target genes were verified by the mRNAs sequencing results at the same time point. Finally, 182 target genes were identified as likely to be networked regulated by the 38 different miRNAs. GO and KEGG enrichment analysis found that miRNAs targeted gene regulation of many key pathways, such as membrane tissue transport, ribosome function, lipid binding, and peroxidase activity. The PPI network analysis showed that miRNAs were involved in SCI repair through complex network regulation, among which dre-miR-21 may enhance cell reversibility through nop56, and that dre-miR-125c regulates axon growth through kpnb1 to repair SCI.
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MicroRNAs , Traumatismos da Medula Espinal , Peixe-Zebra , Animais , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Redes Reguladoras de Genes , LocomoçãoRESUMO
Background: Despite multimodality therapies, the prognosis of patients with malignant brain tumors remains extremely poor. One of the major obstacles that hinders development of effective therapies is the limited availability of clinically relevant and biologically accurate (CRBA) mouse models. Methods: We have developed a freehand surgical technique that allows for rapid and safe injection of fresh human brain tumor specimens directly into the matching locations (cerebrum, cerebellum, or brainstem) in the brains of SCID mice. Results: Using this technique, we successfully developed 188 PDOX models from 408 brain tumor patient samples (both high-and low-grade) with a success rate of 72.3% in high-grade glioma, 64.2% in medulloblastoma, 50% in ATRT, 33.8% in ependymoma, and 11.6% in low-grade gliomas. Detailed characterization confirmed their replication of the histopathological and genetic abnormalities of the original patient tumors. Conclusions: The protocol is easy to follow, without a sterotactic frame, in order to generate large cohorts of tumor-bearing mice to meet the needs of biological studies and preclinical drug testing.
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BACKGROUND: The current literature shows that dyslipidemia can lead to a higher incidence of rotator cuff tears (RCTs) and an increased retear rate after repair. We aimed to evaluate the influence of preoperative dyslipidemia on postoperative pain, patient-reported outcomes (PROs), active range of motion (ROM), and structural integrity. METHODS: A cohort of 111 patients who underwent arthroscopic RCT repair between January 2021 and July 2022, and whose complete preoperative serum lipid data were available within one week prior to surgery was retrospectively reviewed. Dyslipidemia was defined as the presence of an increase or decrease in at least one blood lipid profile (triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, or non-high-density lipoprotein). There were 43 patients in the dyslipidemia group and 68 in the ortholiposis group. Patient evaluations, including pain score, PROs, and ROMs, were conducted preoperatively; at 3 and 6 months postoperatively; and at the last follow-up. Structural integrity was assessed by magnetic resonance imaging (MRI) 6 months after surgery if possible, and Sugaya type 4 or 5 was considered a retear. Propensity score matching (PSM) was used to reduce bias. RESULTS: The RCT size, surgical technique, preoperative pain status, PROs, and active ROM were comparable between patients with dyslipidemia and those with ortholiposis. Three months after surgery, patients in the dyslipidemia group had worse average PROs (Constant score: P = 0.001; ASES score: P = 0.012; UCLA score: P = 0.015), forward flexion (P = 0.012), and internal rotation (P = 0.001) than patients in the ortholiposis group did. The difference between the two groups persisted after PSM but disappeared at the sixth month after surgery. No significant differences in pain score, PROs, or active ROMs were detected between the dyslipidemia and ortholiposis groups after a mean follow-up of 24 months. Of the 72 patients who underwent MRI, 4 retears (5.6%) were found, and all were in the ortholiposis group. There was no difference in the rate of retears between the two groups (P = 0.291) or with (P = 0.495) PSM. CONCLUSIONS: In conclusion, we found that perioperative dyslipidemia may impact initial recovery within the first 3 months following arthroscopic rotator cuff repair but may have no effect on pain, PROs, or active ROMs at a mean 2-year follow-up or rotator cuff integrity at 6 months postoperatively. Trail registration Retrospectively registered.
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Dislipidemias , Lesões do Manguito Rotador , Humanos , Manguito Rotador/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/cirurgia , Artroscopia/métodos , Imageamento por Ressonância Magnética , Amplitude de Movimento Articular , Dor Pós-Operatória/etiologia , LipídeosRESUMO
Researchers have reported that miR-124-3p is highly expressed in patients with chronic endometritis. However, the underlying mechanism of miR-124-3p in the development of endometritis remains unclear. This study constructed an in vitro endometrial cell injury model by treating HEECs with 2 µg/mL LPS for 48 h. Then, 1 mg/kg LPS was injected into both sides of the mouse uterus to construct an in vivo endometrial injury model. The expression of miR-124-3p in human endometrial epithelial cells (HEECs) was assessed using RTâqPCR. Exosomes were separated from bone marrow-derived mesenchymal stem cells (BMSCs) and cocultured with HEECs. A dual-luciferase reporter assay was performed to confirm the relationship between miR-124-3p and DUSP6. The results indicated that LPS inhibited HEEC viability in a time- and dose-dependent manner. The miR-124-3p inhibitor reversed the LPS-induced apoptosis and inhibition of HEEC viability. In addition, miR-124-3p could be transferred from BMSCs to HEECs by exosomes. Exosomes were derived from BMSCs treated with an NC inhibitor (BMSCs/NC Exo) or miR-124-3p inhibitor (BMSCs/anti-miR-124-3p Exo). In addition, BMSCs/anti-miR-124-3p Exo abolished the LPS-induced inhibition of HEEC viability and proliferation by inducing HEEC apoptosis. Moreover, BMSCs/anti-miR-124-3p Exo alleviated the LPS-induced inflammation of HEECs by upregulating DUSP6 and downregulating p-p65 and p-ERK. Furthermore, in an LPS-induced in vivo endometrial injury model, BMSCs/anti-miR-124-3p Exo increased the expression level of DUSP6 and decreased the expression levels of p-p65 and p-ERK. BMSCs/anti-miR-124-3p Exo protected against LPS-induced endometrial damage in vitro and in vivo by upregulating DUSP6 and downregulating p-p65 and p-ERK1/2. This study showed that BMSCs/anti-miR-124-3p Exo might be a potential alternative for the treatment of endometritis.
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Endometrite , Exossomos , MicroRNAs , Feminino , Animais , Camundongos , Humanos , Antagomirs , Lipopolissacarídeos/toxicidade , Endometrite/induzido quimicamente , Endometrite/terapia , MicroRNAs/genéticaRESUMO
As a critical epigenetic modulator of gene expression, histone deacetylases (HDACs) have been involved in the pathogenesis and therapeutic investigation of cancer. Quinolizidine alkaloid sophoridine is known to have anticancer efficacy but with limited indication. By incorporating the pharmacophore of the HDAC inhibitor into the ring-opened sophoridine core, a new series of sophoridine hydroxamic acid derivatives were synthesized. After structure-activity studies, a selected compound was found to exert significant cytotoxicity in triple-negative breast cancer CAL-51 cells (IC50 1.17â µM), and demonstrated low nanomolar inhibitory potency toward HDAC1/3/6. Cellular functional assays indicated that this compound was able to induce apoptosis and cause accumulation of cells in the S phase of the cell cycle. Western blot analysis revealed it to decrease the expression of DNMT1, DNMT3a and DNMT3b by down-regulating phosphor-ERK1/2. Furthermore, treatment with this compound proved to block the PI3K/AKT/mTOR signaling in the PI3KCA and PTEN-mutant CAL-51 cells. Collectively, this work provides a novel lead compound for the development of potential therapeutics against triple-negative breast cancers, possibly mesenchymal-like subtype.
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Antineoplásicos , Neoplasias de Mama Triplo Negativas , Humanos , Inibidores de Histona Desacetilases/farmacologia , Matrinas , Alcaloides Quinolizidínicos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Linhagem Celular Tumoral , Fosfatidilinositol 3-Quinases/metabolismo , Ácidos Hidroxâmicos/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de Células , Histona Desacetilase 1 , Relação Estrutura-Atividade , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
In recent years, extreme weather events have become increasingly frequent, and low winter temperatures have had a significant impact on peach cultivation. The selection of cold-resistant peach varieties is an effective solution to mitigate freezing damage. To comprehensively and accurately evaluate the cold resistance of peaches and screen for high cold resistance among Gansu local resources, nine different types of peach were selected as test resources to assess physiological, biochemical, and anatomical indices. Subsequently, 28 peach germplasms were evaluated using relevant indices. The semi-lethal temperature (LT50) was calculated by fitting the change curve of the electrolyte leakage index (ELI) with the Logistic equation; this can be used as an important index for identifying and evaluating the cold resistance of peach trees. The LT50 values ranged from -28.22 °C to -17.22 °C among the 28 tested resources; Dingjiaba Liguang Tao exhibited the lowest LT50 value at -28.22 °C, indicating its high level of cold resistance. The LT50 was positively correlated with the ELI and malondialdehyde (MDA) content with correlation coefficients of 0.894 and 0.863, respectively, while it was negatively correlated with the soluble sugar (SS), soluble protein (SP), and free proline (Pro) contents with correlation coefficients of -0.894, -0.721, and -0.863, respectively. The thicknesses of the xylem, cork layer, cork layer ratio (CLR) and thickness/cortex thickness (X/C) showed negative correlations (-0.694, -0.741, -0.822, -0.814, respectively). Finally, the membership function method was used to evaluate cold resistance based on the ELI, MDA, Pro, SP, SS, CLR, and xylem thickness/cortex thickness (X/C) indices. The average membership degree among all tested resources ranged from 0.17 to 0.61. Dingjiaba Liguang Tao emerged prominently in terms of high-cold-resistance (HR) membership value (0.61).
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Herbivorous insects having variable numbers of generations annually depending on climate and day length conditions are increasingly breeding additional generations driven by elevated temperature under the scenario of global warming, which will increase insect abundance and result in more frequent damage events. Theoretically, this relies on two premises, i.e., either an evolutionary shift to facultative diapause for an insect behaving an obligatory diapause or developmental plasticity to alter voltinism productively for an insect with facultative diapause before shortening photoperiods inducing diapause. Inter-population evidence supporting the premise (theory) comes primarily from a model system with voltinism linked to thermal gradients across latitude. We examined the intra-population evidence in the field (47°24' N, 123°68' E) with Ostrinia furnacalis, one of the most destructive pests, on corn in Asia and Pacific islands. The species was univoltine in high latitudinal areas (≤46° N). Divergence of the diapause feature (obligatory and facultative) was observed within the field populations from 2016 to 2021. Warmer climates would provoke more facultative diapause individuals to initiate a second generation, which will significantly drive the population to evolve toward facultative diapause (multi-voltinism). Both divergent diapause and temperature must be considered for accurate prediction of phenology and population dynamics in ACB.
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BACKGROUND: Pancreatic intraepithelial neoplasia (PanIN) is the most common precursor lesion of pancreatic ductal adenocarcinoma (PDAC), which is a highly malignant tumor and lack of effective treatment. Although Xiao Chai Hu Tang (XCHT) has a good therapeutic effect on pancreatic cancer patients with advanced stage, the effect and mechanism of XCHT remains unclear in pancreatic tumorigenesis. PURPOSE: To assess the therapeutic effects of XCHT on the malignant transformation from PanIN to PDAC and to reveal its mechanisms of pancreatic tumorigenesis. METHODS: Syrian golden hamster were induced by N-Nitrosobis (2-oxopropyl) amine (BOP) to establish the pancreatic tumorigenesis model. The morphological changes of pancreatic tissue were observed by H&E and Masson staining; the Gene ontology (GO) analysis the transcriptional profiling changes; the mitochondrial ATP generation, mitochondrial redox status, mitochondrial DNA (mtDNA) N6-methyladenine (6mA) level and relative mtDNA genes expressions were examined. In addition, immunofluorescence detect the cell localization of 6mA in human pancreatic cancer PANC1 cell. Using the TCGA database, the prognostic effect of mtDNA 6mA demethylation ALKBH1 expression on pancreatic cancer patients was analyzed. RESULTS: We confirmed the mtDNA 6mA levels were gradually increased with the mitochondrial dysfunction in PanINs progression. XCHT showed the effect to inhibit the occurrence and development of pancreatic cancer in Syrian hamster pancreatic tumorigenesis model. In addition, the lack of ALKBH1 mediated mtDNA 6mA increase, mtDNA coded genes down-expression and abnormal redox status were rescued by XCHT. CONCLUSIONS: ALKBH1/mtDNA 6mA mediated mitochondrial dysfunction to induce the occurrence and progression of pancreatic cancer. XCHT can improve ALKBH1 expression and mtDNA 6mA level, regulate the oxidative stress and expression of mtDNA coded genes. This study investigated a new molecular mechanism of pancreatic tumorigenesis, and revealed the therapeutic efficacy of XCHT in pancreatic tumorigenesis for the first time.
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Bupleurum , Neoplasias Pancreáticas , Animais , Cricetinae , Humanos , DNA Mitocondrial/genética , Mesocricetus , Carcinogênese , Transformação Celular Neoplásica , Neoplasias Pancreáticas/induzido quimicamente , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Mitocôndrias , Homólogo AlkB 1 da Histona H2a Dioxigenase , Neoplasias PancreáticasRESUMO
BACKGROUND: Effective analgesia is required to ensure maternal and neonatal safety. OBJECTIVE: To compare the therapeutic effects of analgesia applied throughout labor and analgesia applied during the first stage of labor in women with pregnancy-induced hypertension (PIH). METHODS: In this study, 120 puerperae with PIH who gave birth in our hospital were enrolled as the study participants and were randomized into two groups (n= 60 in each group) using a coin flip. Those who received analgesia throughout labor were enrolled in the observation group, and those administered analgesia during the first stage of labor were enrolled in the control group. The analgesic effects, changes in blood pressure during labor, and neonatal health were compared between the two groups. RESULTS: Differences in visual analog scale (VAS) scores before analgesia, 10 min after analgesia, and full cervical dilation between the two groups were not statistically significant (P> 0.05 in all). The VAS scores of the puerperae in the observation group during forced breathing in the second stage of labor and fetal head expulsion were lower than those in the control group (P< 0.05 for both). The incidence of postpartum hemorrhage, forceps delivery, and antihypertensive treatment in the observation group was slightly lower than in the control group, but the differences were not statistically significant (P> 0.05). The rate of oxytocin treatment in puerperae in the observation group was significantly lower than in the control group (P< 0.05). The differences in base excess, arterial partial pressure of oxygen, partial pressure of carbon dioxide, and pH between the two groups of newborns were not statistically significant (P> 0.05 for all). Differences in changes in systolic and diastolic blood pressure between the two groups of puerperae were not statistically significant (P> 0.05 for both). Eclampsia did not occur during labor in either group. CONCLUSION: For patients with PIH, the application of analgesia throughout labor had a positive analgesic effect, effectively controlling the changes in blood pressure and ensuring the health of newborns. This is worthy of widespread clinical application.
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Analgesia , Hipertensão Induzida pela Gravidez , Trabalho de Parto , Feminino , Humanos , Recém-Nascido , Gravidez , Analgesia/efeitos adversos , Analgésicos/farmacologia , Parto Obstétrico , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Trabalho de Parto/efeitos dos fármacos , Dor , AdultoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Xiao Chai Hu Tang (XCHT) derived from the classic medical book Shang Han Lun (Treatise on Febrile Diseases) in the Eastern Han Dynasty, which has been widely used in China and other Asian countries for the treatment of inflammation and fibrosis of chronic pancreatitis (CP), but the therapeutic mechanism of XCHT in pancreatic fibrosis remains unclear. AIM OF THE STUDY: This study aimed to evaluate the intervention effects and explore pharmacological mechanism of XCHT on inflammation and fibrosis in cerulein-induced CP model. MATERIALS AND METHODS: Fifty male C57BL/6 mice were randomly divided into five main groups, 10 animals in each: Control, CP model (50 µg/kg cerulein), high dose XCHT-treated CP group (60 g/kg XCHT), medium dose XCHT-treated CP group (30 g/kg XCHT) and low dose XCHT-treated CP group (15 g/kg XCHT). Different doses of XCHT were given to mice by gavage twice a day for 2 weeks after the CP model induction. Pancreatic tissues were harvested and the pancreatic inflammation and fibrosis were evaluated by histological score, Sirius red staining, and alpha-smooth muscle actin (α-SMA) immunohistochemical staining. ELISA, IHC and RT-qPCR were performed to detect the expression of Vitamin D3 (VD3) and Vitamin D receptor (VDR) in serum and pancreatic tissues, respectively. The expressions of NLRP3 inflammasome related genes and molecules were assayed by WB, IHC and RT-qPCR. RESULTS: The pathohistological results demonstrated that XCHT markedly inhibited the fibrosis and chronic inflammation of cerulein-induced CP, indicated by reduction of collagen I, collagen III, α-SMA, and NLRP3 expressions. XCHT significantly increased VD3 and VDR expression while reduced the pancreatic NLRP3 expression. Correspondingly, XCHT decreased the levels of NLRP3 downstream targets IL-1ß, TNF-α and IL-6. CONCLUSIONS: These results revealed that XCHT suppressed the pancreatic fibrosis and chronic inflammation in cerulein-induced CP model by enhancing the VD3/VDR expression and inhibiting the secretion of NLRP3-assoicated inflammatory factors.
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Ceruletídeo , Pancreatite Crônica , Actinas/metabolismo , Animais , Ceruletídeo/efeitos adversos , Colágeno/metabolismo , Modelos Animais de Doenças , Fibrose , Inflamassomos/metabolismo , Inflamação , Interleucina-6 , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pancreatite Crônica/induzido quimicamente , Pancreatite Crônica/tratamento farmacológico , Pancreatite Crônica/metabolismo , Receptores de Calcitriol/uso terapêutico , Transdução de Sinais , Fator de Necrose Tumoral alfa , Vitamina D/efeitos adversosRESUMO
The hazardous waste penicillin fermentation residue (PR) is a huge hazard to the environment. The bio-oil produced by the pyrolysis of the penicillin fermentation residue has the potential to become a biofuel in the future. This paper studied the pyrolysis characteristics of PR at 400°C â¼700°C. According to the weight loss and weight loss rate of PR, the whole process of pyrolysis can be divided into three stages for analysis: dehydration and volatilization, initial pyrolysis, and pyrolytic char formation. The experimental results showed that the yield of the liquid phase is the highest (33.11%) at 600°C. GC-MS analysis results showed that high temperature is beneficial to reduce the generation of oxygenated hydrocarbons (73%â¼31%) and the yield of nitrogenous compounds gradually increased (19%â¼43%); the yield of hydrocarbons was low in 400°Câ¼600°C pyrolysis (2%â¼5%) but significantly increased around 700°C (22%). In the temperature range of 400°C to 700°C, the proportion of C5-C13 in bio-oil gradually increased (26%-64%), and the proportion of C14-C22 gradually decreased (47%-16%). The catalyst can increase the proportion of hydrocarbons in the bio-oil component. And the Fe2O3/HZSM-5 mixed catalyst has a significant reduction effect on oxygen-containing hydrocarbons and nitrogen-containing compounds.
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Penicilinas , Pirólise , Fermentação , Temperatura Alta , Hidrocarbonetos , Catálise , BiocombustíveisRESUMO
Antibiotics and antibiotic resistance genes (ARGs) are enriched in antibiotic fermentation residues (AFRs). In this study, we investigated the effect of hydrothermal treatment on dewatering, biogas production, and removal of ARGs in the penicillin fermentation residue (PFR). Solid, 120 µm particles in the PFR were disintegrated to 30 - 40 µm after 140 - 180 °C hydrothermal range. Of extracellular polymeric substance, 79.8 ± 0.4% was decomposed to release 82.2 ± 0.6% of bound water at 180 °C. The effective solid-liquid separation was achieved only after a hydrothermal treatment of 180 °C. More than 75% of organic matter in the filtrate was transformed into biogas by the upflow anaerobic sludge blanket (UASB). The absolute abundance of 16 S rRNA and ARGs decreased by 2.4 - 5.2 logs after hydrothermal treatment. The ratio of extracellular ARGs (eARGs) to total ARGs increased at 80 °C and decreased at higher temperature (>120 °C). The absolute abundance of ARGs increased by 0.7 - 1.6 logs in anaerobic digestion, and the relative abundances of ARGs based on 16 S rRNA plummeted by 3 logs. Most (98.7 ± 0.4%) ARGs were distributed in suspended solids and were removed by membrane filtration. Hydrothermal treatment demonstrated broad applicability to 10 varieties of AFRs.
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Antibacterianos , Biocombustíveis , Anaerobiose , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Matriz Extracelular de Substâncias Poliméricas , Fermentação , Genes Bacterianos , Esgotos , Águas ResiduáriasRESUMO
Various pollutants are released during pharmaceutical production processes, which is of great concern. Most studies have focused on the terminal treatment results of mixed pharmaceutical wastewater, and further research on wastewater from the production processes is required. This study investigated the wastewater quality indicators, residual antibiotics, and biological toxicity of the wastewater during the production process in a large pharmaceutical producing factory in Northern China. The wastewater contained numerous organic pollutants, with the chemical oxygen demand (COD) values ranging from 2.0 × 103 to 2.6 × 105 mg L-1 and the total nitrogen (TN) values ranging from 1.3 × 103 to 2.0 × 104 mg L-1. High concentrations of cephalexin and cefradine remained in the wastewater of the production workshop, with the highest concentration of cefradine reaching 1328 mg L-1. The wastewater from the oxidation and solvent recovery workshops was more toxic to Vibrio fischeri and Daphnia magna than that of other workshops. Moreover, the biological acute toxicity of wastewater was significantly correlated with the concentration of COD and TN (p < 0.01). This study provides new insights into the treatment of antibiotic production wastewater, illuminating the incomplete extraction of products and the significant risk posed by pharmaceutical wastewater to the environment.
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Preparações Farmacêuticas , Poluentes Químicos da Água , Aliivibrio fischeri , Animais , Antibacterianos/toxicidade , Daphnia , Eliminação de Resíduos Líquidos , Águas Residuárias , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidadeRESUMO
Glucocorticoid-induced cataract (GIC)-associated biomarkers were screened by ceRNA network construction. The GIC samples' GSE3040 were obtained from the NCBI-GEO database. R's Limma package was used to identify differentially expressed RNAs (DERs) between the normal and GIC samples group (4- and 16-h). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis for the mRNAs in the constructed GIC lncRNA-miRNA-mRNA ceRNA regulation network was implemented. A total of 1665 and 1443 DERs were obtained in the 4- and 16-h group, respectively. At two time points, 256 overlapping DERs were identified, of which 210 (17 lncRNAs and 203 mRNAs) had significant differential expression (4 down- and 206 up-regulated). A total of 534 co-expressed ligation pairs (all up-regulated) were obtained. A ceRNA regulation network was constructed. RPS6KA5, GAB1, CCR7, CCL2, COL4A4, and PPARG were obtained and significantly enriched in the 4 KEGG signaling pathways and were featured as GIC target molecules.
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Catarata , MicroRNAs , RNA Longo não Codificante , Catarata/induzido quimicamente , Catarata/genética , Redes Reguladoras de Genes , Glucocorticoides , Humanos , RNA Longo não Codificante/genéticaRESUMO
In order to improve the antitumor potency and therapeutic margins of natural product sophoridine, its novel nitrogen mustard carbamate derivatives were designed and synthesized. In screening their inâ vitro activity, we found all the tested compounds were more potent against the highly aggressive triple-negative breast cancer cell line MDA-MB-231. Cellular functional assays showed that representative compounds could induce G1-phase arrest and trigger apoptosis, evidenced by the alteration of Bax, Bcl-2, caspase-3 and PARP levels. Furthermore, these compounds significantly enhanced the autophagic flux with increased expression of LC3-II and Beclin-1, as well as decreased level of p62, which may attribute to simultaneously inhibition of the phosphorylation of p70S6K, 4E-BP1 and AKT, the key substrates of the mTOR signaling pathway. In vivo, two compounds revealed potent antitumor activity in mice bearing MDA-MB-231. Altogether, our work describes novel leads to yield more potent chemotherapeutics against triple-negative breast cancers, possibly mesenchymal stem-like subtype.
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Alcaloides/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Quinolizinas/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Alcaloides/síntese química , Alcaloides/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Estrutura Molecular , Quinolizinas/síntese química , Quinolizinas/química , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Serina-Treonina Quinases TOR/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , MatrinasRESUMO
Antibiotic fermentation residue (AR) is composed of hazardous organic waste produced by the pharmaceutical industry. AR can be effectively converted into bio-oil by fast pyrolysis, but its high nitrogen content limits the prospect of bio-oil as a fuel resource. In order to further reduce the nitrogen content of AR bio-oil, we have examined the catalytic removal of N and O from penicillin fermentation residue (PR) bio-oil under fast pyrolysis conditions. We have used M/HZSM-5 (M = Fe, Co, Ni, Cu, Zn, Zr, Mo, Ag and Ce) metal catalysts, with a metal oxide content of 10%. Additionally, the effect of mixed and separated catalytic forms on catalytic upgrading were analyzed, and changes in the catalyst itself before and after pyrolysis under separated catalytic conditions were specifically investigated. Our results show that the metal elements in the fresh catalyst will exist in the form of oxides, ions and simple metals. In-situ reduction caused by pyrolysis gas in the catalytic pyrolysis process makes some ionic metals (e.g., Co2+, Cu2+ and Ag+) in the catalyst transform into oxides, and some metal oxides are reduced to simple metals or suboxides (including Fe, Ni, Cu and Mo). The N content in the mixed catalytic bio-oil decreased from 10.09 wt% to Zn/HZSM-5 (6.98 wt%), Co/HZSM-5 (7.1 wt%), Cu/HZSM-5 (7.18 wt%) and Ce/HZSM-5 (7.18 wt%). We also observed significant reduction in the O content (9.77 wt%) with Ag/HZSM-5 (3.75 wt%), Mo/HZSM-5 (6.86 wt%), Ce/HZSM-5 (8.39 wt%) and Fe/HZSM-5 (8.54 wt%) in the separated catalytic bio-oil. The Ni/HZSM-5 catalystcan reduce the organic acid content in bio-oil from 22.9% to 10.8%. The separated catalysis methodology also promoted an increase of hydrocarbons in the bio-oil: Zn/HZSM-5, Ag/HZSM-5, Mo/HZSM-5, Zr/HZSM-5 and Ce/HZSM-5 reached 11.6%, 11.5%, 11.1%, 10.1%, and 8.8%, respectively. Carbon deposition formed by aromatic carbon/graphite carbon, pyrrole and pyridine compounds leads to deactivation of the catalyst.
Assuntos
Biocombustíveis , Penicilinas , Biomassa , Catálise , Fermentação , Temperatura Alta , Óleos de Plantas , PolifenóisRESUMO
Hydrothermal liquefaction (HTL) of biomass used HTL reaction under high temperature and pressure to produce bio-oil. This technology is considered as one of the most promising converting technology of biomass to biofuels. This paper summarized current research developments of HTL for bio-oil and analyzed its reaction mechanism and influencing factors based on bibliometric analysis. The results showed that reaction conditions and catalyst have been still global researching focuses about HTL. Compared with homogeneous catalysts, the study of HTL by using heterogeneous catalyst developed more quickly. With promotion of resource recovering, food waste, sludge, and other organic waste can also be used as raw materials for HTL for bio-oil now. The structure of this paper was shown in graphic abstract. Firstly, bibliometric analysis was conducted on hydrothermal liquefaction for bio-oil production. According to the emergency frequency of key words, catalyst, microalgae, reaction conditions, and biomass waste as raw material for hydrothermal liquefaction were determined as four parts of the paper. Finally, we speculated the development trend of hydrothermal liquefaction for bio-oil production.
Assuntos
Alimentos , Eliminação de Resíduos , Bibliometria , Biocombustíveis , Biomassa , Óleos de Plantas , Polifenóis , Temperatura , ÁguaRESUMO
In this study, the antibiotic residue was used as a raw material to catalyze hydrothermal liquefaction (HTL) in an ethanol-water system to prepare bio-oil. The study explored the effects of ethanol-water ratio and three kinds of molecular sieve catalysts (HZSM-5, MCM-41, and γ-Al2O3) on the yield and characterization of bio-oil. The experimental results showed that the highest bio-oil yield was obtained at the ethanol-water ratio of 1 : 1 and the three kinds of molecular sieve catalysts of 15%. GC-MS, 1H NMR, TGA, and CHNS were used for the characterization of bio-oil. Higher carbon (up to 71.44%), hydrogen (up to 9.376%), and a high heating value (HHV, 34.714 MJ kg-1) were observed for catalytically liquefied bio-oil compared to non-catalytically liquefied bio-oil. The analysis of aqueous phase products indicated the existence of valuable nutrients. Besides, the reusability of three kinds of molecular sieve catalysts indicated that catalysts could be successfully reused several times and continuously exhibited the catalyst effect.