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Background: Pesticides are widely used in agricultural activities. Although pesticide use is known to cause damage to the human body, its relationship with thyroid function remains unclear. Therefore, this study aimed to investigate the association between pesticide exposure and thyroid function. Methods: The Chinese database used included 60 patients with pyrethroid poisoning and 60 participants who underwent health checkups between June 2022 and June 2023. The NHANES database included 1,315 adults enrolled from 2007 to 2012. The assessed pesticide and their metabolites included 2,4-dichlorophenoxyacetic acid (2,4-D), 4-fluoro-3-phenoxybenzoic acid (4F3PB), para-nitrophenol (PN), 3-phenoxybenzoic acid (3P), and trans-dichlorovinyl-dimethylcyclopropane carboxylic acid (TDDC). The evaluated indicators of thyroid function were measured by the blood from the included population. The relationship between pesticide exposure and thyroid function indexes was investigated using linear regression, Bayesian kernel machine regression (BKMR), restricted cubic spline (RCS), and weighted quantile sum (WQS) models. Results: The Chinese data showed that pesticide exposure was negatively correlated with the thyroid function indicators FT4, TT4, TgAb, and TPOAb (all p < 0.05). The BKMR model analysis of the NHANES data showed that the metabolic mixture of multiple pesticides was negatively associated with FT4, TSH, and Tg, similar to the Chinese database findings. Additionally, linear regression analysis demonstrated positive correlations between 2,4-D and FT3 (p = 0.041) and 4F3PB and FT4 (p = 0.003), whereas negative associations were observed between 4F3PB and Tg (p = 0.001), 4F3PB and TgAb (p = 0.006), 3P and TgAB (p = 0.006), 3P and TPOAb (p = 0.03), PN and TSH (p = 0.003), PN and TT4 (p = 0.031), and TDDC and TPOAb (p < 0.001). RCS curves highlighted that most pesticide metabolites were negatively correlated with thyroid function indicators. Finally, WQS model analysis revealed significant differences in the weights of different pesticide metabolites on the thyroid function indexes. Conclusion: There is a significant negative correlation between pesticide metabolites and thyroid function indicators, and the influence weights of different pesticide metabolites on thyroid function indicators are significantly different. More research is needed to further validate the association between different pesticide metabolites and thyroid disease.
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Encuestas Nutricionales , Plaguicidas , Pruebas de Función de la Tiroides , Glándula Tiroides , Humanos , Masculino , Femenino , Persona de Mediana Edad , China , Adulto , Glándula Tiroides/efectos de los fármacos , Exposición a Riesgos Ambientales/efectos adversos , Bases de Datos Factuales , Anciano , Ácido 2,4-Diclorofenoxiacético , Pueblos del Este de AsiaRESUMEN
Porcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen that causes severe abortions in sows and high piglet mortality, resulting in huge economic losses to the pig industry worldwide. The emerging and novel PRRSV isolates are clinically and biologically important, as there are likely recombination and pathogenic differences among PRRSV genomes. Furthermore, the NADC34-like strain has become a major epidemic strain in some parts of China, but the characterization and pathogenicity of the latest strain in Inner Mongolia have not been reported in detail. In this study, an NADC34-like strain (CHNMGKL1-2304) from Tongliao City, Inner Mongolia was successfully isolated and characterized, and confirmed the pathogenicity in pigs. The phylogenetic tree showed that this strain belonged to sublineage 1.5 and had high homology with the strain JS2021NADC34. There is no recombination between CHNMGKL1-2304 and any other domestic strains. Animal experiments show that the CHNMGKL1-2304 strain is moderately virulent to piglets, which show persistent fever, weight loss and high morbidity but no mortality. The presence of PRRSV nucleic acids was detected in both blood, tissues, nasal and fecal swabs. In addition, obvious pathological changes and positive signals were observed in lung, lymph node, liver and spleen tissues when subjected to hematoxylin-eosin (HE) staining and immunohistochemistry (IHC). This report can provide a basis for epidemiological investigations and subsequent studies of PRRSV.
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Genoma Viral , Filogenia , Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Animales , Porcinos , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Virus del Síndrome Respiratorio y Reproductivo Porcino/patogenicidad , Virus del Síndrome Respiratorio y Reproductivo Porcino/aislamiento & purificación , Virus del Síndrome Respiratorio y Reproductivo Porcino/clasificación , China , Síndrome Respiratorio y de la Reproducción Porcina/virología , Síndrome Respiratorio y de la Reproducción Porcina/patología , Virulencia , Evolución MolecularRESUMEN
OBJECTIVE: This study explored the molecular mechanisms by which dexmedetomidine (Dex) alleviates cisplatin (CP)-induced acute kidney injury (AKI) in rats. METHODS: CP-induced AKI models were established, and Dex was intraperitoneally injected at different concentrations into rats in the model groups. Subsequently, rats were assigned to the control, CP, CP + Dex 10 µg/kg, and CP + Dex 25 µg/kg groups. After weighing the kidneys of the rats, the kidney arterial resistive index was calculated, and CP-induced AKI was evaluated. In addition, four serum biochemical indices were measured: histopathological damage in rat kidneys was detected; levels of inflammatory factors, interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor alpha, in kidney tissue homogenate of rats were assessed through enzyme-linked immunosorbent assay (ELISA); and levels of NLRP-3, caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N in kidney tissues of rats were determined via western blotting. RESULTS: Dex treatment reduced nephromegaly and serum clinical marker upregulation caused by CP-induced AKI. In addition, hematoxylin and eosin staining revealed that Dex treatment relieved CP-induced kidney tissue injury in AKI rats. ELISA analyses demonstrated that Dex treatment reduced the upregulated levels of proinflammatory cytokines in the kidney tissue of AKI rats induced by CP, thereby alleviating kidney tissue injury. Western blotting indicated that Dex alleviated CP-induced AKI by inhibiting pyroptosis mediated by NLRP-3 and caspase-1. CONCLUSION: Dex protected rats from CP-induced AKI, and the mechanism may be related to NLRP-3/Caspase-1-mediated pyroptosis.
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Lesión Renal Aguda , Dexmedetomidina , Ratas , Animales , Dexmedetomidina/efectos adversos , Cisplatino/toxicidad , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/prevención & control , Lesión Renal Aguda/patología , Riñón/patología , Interleucina-1beta , Caspasas/efectos adversosRESUMEN
Purpose: This study compared hidden blood loss (HBL) among three different endoscopic spinal procedures and investigated its risk factors. Patients and methods: This single-centre retrospective analysis collected data from consecutive hospitalized patients with single-segment lumbar disc herniation (LDH) undergoing unilateral biportal endoscopic discectomy (UBE), percutaneous endoscopic transforaminal discectomy (PETD), or percutaneous endoscopic interlaminar discectomy (PEID) from December 2020 to October 2022. HBL was calculated using Nadler's and Gross's formulas. The authors used Pearson's or Spearman's correlation analysis to explore the relationship between patient characteristics and HBL. Multivariate linear regression analysis was used to identify independent risk factors for HBL. Results: In total, 122 consecutive patients (68 females and 54 males) were enroled in this study. The average HBL was 381.87±218.01 ml in the UBE group, 252.05±118.44 ml in the PETD group and 229.63±143.9 ml in the PEID group (P<0.05). Pearson's or Spearman's correlation analysis showed that operative time, preoperative haemoglobin, preoperative haematocrit, and preoperative Albumin (ALB) were correlated with HBL in the UBE group, while sex, age, operative time, postoperative ALB, and patients' blood volume (PBV) were related to HBL in the PETD group (P<0.05). Operative time and preoperative activated partial thromboplastin time were related to HBL in the PEID group (P<0.05). Multiple linear regression analysis showed a positive correlation between HBL and operative time in all three groups (P<0.001, P<0.001, P<0.05). Conclusion: HBL was higher in the UBE group than in the PETD and PEID groups, and operative time may be a common risk factor for the three groups.
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In this Letter, we propose a novel, to the best of our knowledge, dual-mode tunable absorber that utilizes quasi-bound states in the continuum (q-BIC) based on the periodically arranged silicon cylinders tetramer. By introducing asymmetry perturbation through manipulating the diameters of diagonal cylinders in the all-dielectric structure, the symmetry-protected BIC (SP-BIC) transforms into q-BIC, leading to the emergence of one transmission and one reflection Fano-like resonant mode. The relationship between the quality factor of each mode and the asymmetry parameter α is analyzed, revealing an exponential dependence with an exponent of -1.75, i.e., Q â α-1.75. To explain the underlying physics, multipole decomposition analysis and Aleksandra's theory are applied. Subsequently, a monolayer graphene is introduced to the all-dielectric structure to demonstrate the application of the dual-mode tunable absorber. When the critical coupling condition is satisfied, each mode can achieve the theoretical maximum absorption, demonstrating the distinctive capability of our proposed absorber for tuning and efficient light absorption. This research provides valuable insights into light-matter interactions and opens up possibilities for optical modulation and the development of graphene-based devices.
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BACKGROUND: Given the inconclusive literature on operative time, pain relief, functional outcomes, and complications, this meta-analysis aims to compare the efficacy of Unilateral Biportal Endoscopy (UBE) and Micro-Endoscopic Discectomy (MED) in treating Degenerative Lumbar Spinal Stenosis (DLSS). METHODS: A thorough literature search was conducted in accordance with the PRISMA guidelines and based on the PICO framework. The study interrogated four primary databases-PubMed, Embase, Web of Science, and the Cochrane Library-on August 16, 2023, without time restrictions. The search employed a strategic selection of keywords and was devoid of language barriers. Studies were included based on strict criteria, such as the diagnosis, surgical intervention types, and specific outcome measures. Quality assessment was performed using the Newcastle-Ottawa Scale, and statistical analysis was executed through Stata version 17. RESULTS: The meta-analysis incorporated 9 articles out of an initial yield of 1,136 potential studies. Considerable heterogeneity was observed in surgical duration, but no statistically significant difference was identified (MD = - 2.11, P = 0.56). For VAS scores assessing lumbar and leg pain, UBE was statistically superior to MED (MD = - 0.18, P = 0.013; MD = - 0.15, P = 0.006, respectively). ODI scores demonstrated no significant difference between the two surgical methods (MD = - 0.57, P = 0.26). UBE had a lower incidence of complications compared to those receiving MED (OR = 0.54, P = 0.036). CONCLUSIONS: UBE and MED exhibited comparable surgical durations and disability outcomes as measured by ODI. However, UBE demonstrated superior efficacy in alleviating lumbar and leg pain based on VAS scores. The findings present an intricate evaluation of the two surgical interventions for DLSS, lending valuable insights for clinical decision-making.
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Estenosis Espinal , Humanos , Estenosis Espinal/diagnóstico por imagen , Estenosis Espinal/cirugía , Endoscopía , Discectomía , Evaluación de Resultado en la Atención de Salud , Dolor/cirugía , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
Background: This study aimed to investigate putative causal effects between constipation and stroke using bidirectional Mendelian randomization (MR) analysis. Methods: Based on the cross-sectional study, logistic regression models were developed to assess the association between constipation and stroke prevalence. Subsequently, genome-wide association studies statistics were employed to perform MR analysis between constipation and stroke, as well as its subtypes. The inverse variance weighting (IVW) method was the primary method, complemented by four additional methods, namely weighted median, weighted mode, simple mode, and MR-Egger regression. Cochran's Q test, MR-Egger intercept test, MR Pleiotropy RESidual Sum and Outlier, and MR Steiger test were performed to assess heterogeneity and pleiotropy effects. Results: Constipation was associated with a greater risk of stroke even after adjusting for all covariates in logistic regression [odds ratio (OR) = 1.46, 95% confidence interval (CI) = 1.01-2.09, p = 0.042]. IVW MR analysis revealed that constipation affected large artery atherosclerosis (LAS; IVW OR = 1.5, 95% CI = 1.07-2.104, p = 0.019). No significant or suggestive association was observed with the risk of stroke or its various subtypes in MR analysis. Meanwhile, reverse MR analysis revealed no significant causal relationship between stroke or other stroke subtypes and constipation. The results of sensitivity analyses revealed no significant horizontal pleiotropy affecting causal estimates. Conclusion: While cross-sectional studies have established that constipation increases the risk of stroke, this two-sample bidirectional MR analysis revealed a positive correlation between constipation and LAS. However, no such correlation was observed between constipation and stroke, including its various subtypes.
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This study aimed to explore the biomechanical effects on adjacent vertebra of thoracolumbar Osteoporotic Vertebra Compression Fracture (OVCF) after Percutaneous Kyphoplasty (PKP) with intraoperative intradiscal cement leakage (ICL) by applying a Finite-Element Analysis. We collected pre- and post-operative computer tomography (CT) images of a 71-year-old female patient with single T12 OVCF, who underwent an intraoperative cement leakage into the T12-L1 disc. Three-dimensional finite element models of thoracolumbar spine (T10-L2) were built with the support of Materialise Interactive Medical Image Control System (MIMICS) and ABAQUS software. The stress on adjacent vertebrae and endplates under the uniform compressive pressure (0.3 MPa) and during different loading moments were analyzed. The three-dimensional finite element models reveal an asymmetrical distribution of von Mises stresses on the adjacent endplate unaffected by the surgical intervention. The maximum von Mises stress on adjacent vertebral bodies increased during different loading conditions, especially for lateral bending and rotation loading conditions, whereas the maximum von Mises stress on distal non-treated vertebrae decreased on anteflexion and backward extension loading conditions. Post-operative adjacent vertebra compression fractures after PKP with intraoperative intradiscal cement leakage (ICL) may be closely related to the biomechanical changes of adjacent vertebrae of thoracolumbar OVCF, and it may increase the risk of postoperative fracture.
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Fracturas por Compresión , Cifoplastia , Fracturas de la Columna Vertebral , Femenino , Humanos , Anciano , Fracturas por Compresión/diagnóstico por imagen , Fracturas por Compresión/cirugía , Columna Vertebral , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/cirugía , Cuerpo Vertebral , Cementos para Huesos , Cementos de Ionómero VítreoRESUMEN
INTRODUCTION AND IMPORTANCE: Spinal epidural hematoma (SEH) is an uncommon condition that can result in severe neurological problems and needs to be treated as soon as possible. The incidence of traumatic SEH is 0.5 %-1.7 %, but increases to 9 % in patients with rheumatic diseases. Surgical treatment options include open surgery and minimally invasive surgery. We reported a post-traumatic SEH at T12/L1 level combined with L5 nerve injury and treated by UBE technique. To our knowledge, there was no reported cases like this. CASE PRESENTATION: A 38-year-old man with left leg weakness and severe back pain after fell down while cycling. Physical examination suggested left hip abduction was 2/5 strength, left dorsiflexion of hallux dorsal extension was 0/5 strength and the left ankle dorsiflexion was 2/5 strength. Magnetic resonance images (MRI) of lumbar spine showed a two-leveled hematoma extending from T12 to L1. After 1 year of surgery, the patient's symptoms had largely disappeared and he was able to perform daily activities independently. CLINICAL DISCUSSION: An epidural hematoma at the L1 level is can cause symptoms of the L5 nerve root alone, which may be due to anatomical reasons. Complete removal of the epidural hematoma is necessary to restore the function of the nerve. We report a case of successful removal of an epidural hematoma using the UBE technique with good postoperative results. CONCLUSIONS: The single nerve injury can occur with a thoracolumbar segmental hematoma, and UBE technology could be used to remove epidural hematoma.
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In humans, almost all the cell surface and secreted glycoproteins are modified with complex-type N-glycans. Thus, it is essential to obtain complex-type N-glycans to fully understand the biological properties of glycoproteins. Here, human ß-1,2-N-acetylglucosaminyltransferase II (hGnT-II), a Golgi-localized enzyme integral to complex-type N-glycan biosynthesis, was cloned as a truncated transmembrane form (GnT-II-ΔTM) and heterologously overexpressed in Escherichia coli. Our results showed that hGnT-II could be overexpressed in its soluble form by fusing the truncated enzyme with a thioredoxin (Trx)-tag in the Rosetta-Gami 2 strain. Using the optimized induction conditions, the expression level of recombinant protein was enhanced to yield approximately 4 mg per liter culture after affinity purification. The enzyme exhibited appropriate glycosyltransferase activity, and the calculated Km value was 52.4 µM, similar to the protein expressed in mammalian cells. Furthermore, the effect of MGAT2-CDG mutations on enzyme activity was also measured. These results suggested that the E. coli expression system was capable of the large-scale production of bioactive hGnT-II, which can be used for functional study and effective synthesis of complex-type N-glycans.
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Escherichia coli , N-Acetilglucosaminiltransferasas , Animales , Humanos , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas Recombinantes/genética , N-Acetilglucosaminiltransferasas/metabolismo , Glicoproteínas , Polisacáridos/metabolismo , Mamíferos/metabolismoRESUMEN
Objectives: To validate and compare four tools, the Fracture Risk Assessment Tool (FRAX) without bone mineral density (BMD), Beijing Friendship Hospital Osteoporosis Screening Tool (BFH-OST), Osteoporosis Self-Assessment Tool for Asians (OSTA), and BMD, to identify painful new osteoporotic vertebral fractures (PNOVFs). Methods: A total of 2874 postmenopausal women treated from June 2013 to June 2022 were enrolled and divided into two groups: patients with PNOVFs who underwent percutaneous vertebroplasty (PNOVFs group, n = 644) and community-enrolled females (control group, n = 2230). Magnetic resonance and X-ray imaging were used to confirm the presence of PNOVFs. Dual-energy X-ray absorptiometry was performed to calculate the BMD T-scores. Osteoporosis was diagnosed according to WHO Health Organization criteria. Data on the clinical and demographic risk factors were self-reported using a questionnaire. The ability to identify PNOVFs using FRAX, BFH-OST, OSTA, and BMD scores was evaluated using receiver operating characteristic (ROC) curves. For this evaluation, we calculated the areas under the ROC curves (AUCs), sensitivity, specificity, and optimal cut-off points. Results: There were significant differences in FRAX (without BMD), BFH-OST, OSTA, and BMD T-scores (total hip, femoral neck, and lumbar spine) between the PNOVFs and control groups. Compared with BFH-OST, OSTA, and BMD, the FRAX score had the best identifying value for PNOVFs; the AUC of the FRAX score (optimal cutoff =3.6%) was 0.825, while the sensitivity and specificity were 82.92% and 67.09%, respectively. Conclusion: FRAX may be the preferable tool for identifying PNOVFs in postmenopausal women, while BFH-OST and OSTA can be applied as more simple screening tools for PNOVFs.
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Osteoporosis , Fracturas Osteoporóticas , Humanos , Femenino , Posmenopausia , Medición de Riesgo/métodos , Fracturas Osteoporóticas/diagnóstico , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/etiología , Osteoporosis/diagnóstico , Vértebras Lumbares , DolorRESUMEN
Acute promyelocytic leukemia (APL) has become curable over 95% patients under a complete chemo-free treatment with all-trans retinoic acid (ATRA) and arsenic trioxide in low-risk patients. Minimizing chemotherapy has proven feasible in high-risk patients. We evaluated oral arsenic and ATRA without chemotherapy as an outpatient consolidation therapy and no maintenance for high-risk APL. We conducted a multicenter, single-arm, phase 2 study with consolidation phases. The consolidation therapy included Realgar-Indigo naturalis formula (60 mg/kg daily in an oral divided dose) in a 4-week-on and 4-week-off regimen for 4 cycles and ATRA (25 mg/m2 daily in an oral divided dose) in a 2-week-on and 2-week-off regimen for 7 cycles. The primary end point was the disease-free survival (DFS). Secondary end points included measurable resident disease, overall survival (OS), and safety. A total of 54 participants were enrolled at seven centers from May 2019. The median age was 40 years. At the median follow-up of 13.8 months (through April 2022), estimated 2-year DFS and OS were 94% and 100% in an intention-to-treat analysis. All the patients achieved complete molecular remission at the end of consolidation phase. Two patients relapsed after consolidation with a cumulative incidence of relapse of 6.2%. The majority of adverse events were grade 1-2, and only three grade 3 adverse events were observed. Oral arsenic plus ATRA without chemotherapy was active as a first-line consolidation therapy for high-risk APL.Trial registration: chictr.org.cn number, ChiCTR1900023309.
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Arsénico , Arsenicales , Leucemia Promielocítica Aguda , Humanos , Adulto , Leucemia Promielocítica Aguda/tratamiento farmacológico , Tretinoina/uso terapéutico , Trióxido de Arsénico/uso terapéutico , Trióxido de Arsénico/efectos adversos , Arsénico/uso terapéutico , Resultado del Tratamiento , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Óxidos/uso terapéutico , Arsenicales/efectos adversosRESUMEN
Background: Unilateral biportal endoscopic (UBE) spine surgery is a minimally invasive procedure for treating lumbar disorders. Hidden blood loss (HBL) is easily ignored by surgeons because blood loss is less visible. However, there are limited studies on HBL in UBE spine surgery. This study aimed to evaluate HBL and its possible risk factors in patients undergoing UBE spine surgery. Methods: Patients with lumbar disc herniation or lumbar spinal stenosis who underwent unilateral biportal endoscopic surgery between December 2020 and February 2022 at our hospital were retrospectively analyzed. Patient demographics, blood loss-related parameters, and surgical and radiological information were also collected. Pearson or Spearman correlation analysis was conducted to determine the association between clinical characteristics and HBL. Multivariate linear regression analysis was used to determine the independent risk factors for HBL. Results: Fifty-two patients (17 males and 35 females) were retrospectively enrolled in this study. The mean total blood loss (TBL) volume was 434 ± 212â ml, and the mean HBL volume was 361 ± 217â ml, accounting for 77.9% of the TBL in patients who underwent UBE surgery. Multivariate linear regression analysis revealed that HBL was positively associated with operation time (P = 0.040) and paraspinal muscle thickness at the target level (P = 0.033). Conclusions: The amount of HBL in patients undergoing UBE surgery should not be neglected. Operation time and paraspinal muscle thickness at the target level may be independent risk factors for HBL.
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Background: Neuroinflammation, which is mainly mediated by excessive microglia activation, plays a major role in ischemic stroke. Overactivated microglia secrete numerous inflammatory cytokines, causing excessive inflammatory responses and ultimately exacerbating ischemic brain injury. Hence, compounds that attenuate neuroinflammation could become promising drug candidates for ischemic stroke. Fraxetin has an anti-inflammatory effect in many inflammatory diseases. However, whether it possesses an anti-inflammatory capacity in microglia-mediated neuroinflammation after ischemic brain injury is unknown. Our study aimed to investigate the suppression effect of fraxetin on neuroinflammation in lipopolysaccharide (LPS)-activated microglia and establish whether fraxetin could alleviate ischemic brain injury in a rodent model of ischemic stroke. Methods: For the in vitro experiment, primary microglia were obtained from 1-day-old C57/BL6J mice. The cells were activated with LPS and treated with fraxetin at a non-cytotoxic concentration. Real-time PCR, enzyme-linked immunosorbent assays, and immunofluorescence staining were used to evaluate the anti-inflammatory effects of fraxetin. The potential molecular mechanisms were explored and verified through RNA-sequencing analysis, western blotting and real-time PCR. For the in vivo experiment, focal ischemia was induced by middle cerebral artery occlusion (MCAO) in 8-week-old male C57/BL6J mice. Fraxetin (5 mg/kg) or an equal volume of saline was injected into mice intraperitoneally after MCAO, and 2% 2,3,5-triphenyltetrazolium chloride staining was applied to measure infarct volume. Behavioral tests were conducted to measure neurological deficits in the mice. Real-time PCR, western blotting, and immunofluorescence staining were used to examine the expression of inflammatory cytokines and microglia activation in the ischemic penumbra. Results: Fraxetin effectively inhibited the expression of proinflammatory cytokines including inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1 beta, and interleukin-6 in LPS-activated microglia. Fraxetin also suppressed the PI3K/Akt/NF-κB signaling pathway in activated microglia, which contributed to its anti-inflammatory effects. Furthermore, the administration of fraxetin attenuated ischemic brain injury and behavioral deficits after stroke. Finally, fraxetin was found to attenuate the activation of microglia both in vitro and in vivo. Conclusions: Our results suggest that fraxetin has a suppression effect on microglia-mediated neuroinflammation, and this effect is associated with the PI3K/Akt/NF-κB signaling pathway. Fraxetin may therefore have potential neuroprotective properties for ischemic stroke.
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PURPOSE: The purpose of this study was to identify the incidence, sites and main pathogens, and risk factors for infectious complications occurring in patients with adult acute myeloid leukemia (AML) during the first course of venetoclax combined with decitabine or azacitidine. METHODS: A retrospective cohort analysis was performed of 81 patients with AML older than 14 years who received the first cycle of venetoclax combined with a hypomethylating agent (HMA) between March 2018 and March 2021 at our institution. Infectious complications, if any, were documented. RESULTS: Among a total of 81 cases of AML, 59 (72.8%) patients occurred infections, including fever without an identifiable source (28.8%), clinically documented infections (40.7%), and microbiologically documented infections (30.5%). The most commonly isolated organism in culture was Candida albicans, followed by Klebsiella pneumonia, and Pseudomonas aeruginosa. The 4-week and 8-week mortality rates were 3.7% and 7.4%, respectively. In multivariate analysis, a high proportion of blasts in bone marrow, decreased hemoglobin level, and fever with or without a documented infection at baseline were significant independent risk factors for infectious complications. CONCLUSION: Compared with conventional chemotherapy, the incidence of infectious complications of venetoclax combined with decitabine or azacitidine significantly decreased. Pretreatment high leukemia burden and fever were independent risk factors for infections.
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Azacitidina , Leucemia Mieloide Aguda , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Azacitidina/efectos adversos , Compuestos Bicíclicos Heterocíclicos con Puentes , Decitabina/efectos adversos , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Estudios Retrospectivos , Sulfonamidas , Resultado del TratamientoRESUMEN
BACKGROUND: N-glycosylation is initiated from the biosynthesis of lipid-linked oligosaccharide (LLO) on the endoplasmic reticulum (ER), which is catalyzed by a series of Alg (asparagine-linked glycosylation) proteins. SCOPE OF REVIEW: This review summarizes our recent studies on the enzymology of Alg mannosyltransferases (MTases). We also discuss the membrane topology and physiological importance of several ER cytosolic Alg proteins. MAJOR CONCLUSIONS: Utilizing an efficient prokaryotic protein expression system and a new LC-MS quantitative activity assay, we overexpressed all Alg MTases and performed enzymology studies. Moreover, by reconstituting the LLO pathway, the high-yield chemoenzymatic synthesis of high-mannose-type N-glycans was accomplished using recombinant Alg MTases. GENERAL SIGNIFICANCE: The analysis of the enzymology and topology of Alg MTases has provided valuable biochemical information in the LLO biosynthesis pathway. In addition, an efficient chemoenzymatic strategy that could prepare various oligomannose-type N-glycans in sufficient amounts was established for further biological assays.
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Manosiltransferasas , Saccharomyces cerevisiae , Retículo Endoplásmico/metabolismo , Lipopolisacáridos , Manosiltransferasas/metabolismo , Oligosacáridos/metabolismo , Saccharomyces cerevisiae/metabolismoRESUMEN
N-glycosylation starts with the biosynthesis of lipid-linked oligosaccharide (LLO) on the endoplasmic reticulum (ER). Alg2 mannosyltransferase adds both the α1,3- and α1,6-mannose (Man) onto ManGlcNAc2-pyrophosphate-dolichol (M1Gn2-PDol) in either order to generate the branched M3Gn2-PDol product. The well-studied yeast Alg2 interacts with ER membrane through four hydrophobic domains. Unexpectedly, we show that Alg2 structure has diverged between yeast and humans. Human Alg2 (hAlg2) associates with the ER via a single membrane-binding domain and is markedly more stable in vitro. These properties were exploited to develop a liquid chromatography-mass spectrometry quantitative kinetics assay for studying purified hAlg2. Under physiological conditions, hAlg2 prefers to transfer α1,3-Man onto M1Gn2 before adding the α1,6-Man. However, this bias is altered by an excess of GDP-Man donor or an increased level of M1Gn2 substrate, both of which trigger production of the M2Gn2(α-1,6)-PDol. These results suggest that Alg2 may regulate the LLO biosynthetic pathway by controlling accumulation of M2Gn2 (α-1,6) intermediate.
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Manosiltransferasas , Proteínas de Saccharomyces cerevisiae , Vías Biosintéticas , Dolicoles/metabolismo , Humanos , Lipopolisacáridos , Manosiltransferasas/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMEN
Objective: This study aims to report one case of intraspinal epidural cement leakage caused by a novel percutaneous vesselplasty. Methods: A clinical case report from the Orthopedic center of our hospital and a literature review. A 63-year-old woman with an L2 osteoporotic compression fracture underwent novel kyphoplasty, percutaneous vesselplasty. This rare complication was evaluated through a literature search, and its special types are classified in more detail. Results: The patient was hospitalized with low back pain two weeks after a fall. After auxiliary examination, a new type of percutaneous vesselplasty was performed. After the intraoperative injection of bone cement, bone cement leakage extended along the posterior longitudinal ligament and epidural space. There were no special compression symptoms of the spinal cord, and the prognosis of conservative treatment was good. Conclusion: Although percutaneous vesselplasty is relatively safe and frequent, intraspinal leakage may occur, so sufficient preoperative evaluation, intraoperative continuous fluoroscopic monitoring, and timely evaluation of postoperative images are extremely necessary.
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The Kyrgyz are a trans-border ethnic group, mainly living in Kyrgyzstan. Previous genetic investigations of Central Asian populations have repeatedly investigated the Central Asian Kyrgyz. However, from the standpoint of human evolution and genetic diversity, Northwest Chinese Kyrgyz is one of the more poorly studied populations. In this study, we analyzed the non-recombining portion of the Y-chromosome from 298 male Kyrgyz samples from Xinjiang Uygur Autonomous Region in northwestern China, using a high-resolution analysis of 108 biallelic markers and 17 or 24 STRs. First, via a Y-SNP-based PCA plot, Northwest Chinese Kyrgyz tended to cluster with other Kyrgyz population and are located in the West Asian and Central Asian group. Second, we found that the Northwest Chinese Kyrgyz display a high proportion of Y-lineage R1a1a1b2a2a-Z2125, related to Bronze Age Siberian, and followed by Y-lineage C2b1a3a1-F3796, related to Medieval Niru'un Mongols, such as Uissun tribe from Kazakhs. In these two dominant lineages, two unique recent descent clusters have been detected via NETWORK analysis, respectively, but they have nearly the same TMRCA ages (about 13th-14th centuries). This finding once again shows that the expansions of Mongol Empire had a striking effect on the Central Asian gene pool.
Asunto(s)
Cromosomas Humanos Y , Genética de Población , Pueblo Asiatico/genética , China , Cromosomas Humanos Y/genética , Etnicidad , Haplotipos , Humanos , MasculinoRESUMEN
Heavy metals in farmland soil are one of the most hazardous pollutants in the environment, owing to their universality and irreversibility. Modified biochar has been widely used in the adsorption and immobilization of heavy metals in soil, and its applicability is mainly determined by the types of heavy metals, pollution levels, and soil environmental conditions. Soil pollution is gradually becoming more complex and diversified, and heavy metal pollutants mostly occur in the form of compound pollution. However, most studies have focused on single heavy metal pollutant or the addition of heavy metal to soil. This study used rice straw as a raw material to prepare biochar, and modified it with K3PO4, KMnO4, and NaOH. The physicochemical and structural characteristics of the modified biochars were detected using a BET accelerated surface area and porosimetry system, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and the biochars were then analyzed for the availability and forms of Cd and Cu in soils contaminated with heavy metals in the mining area. The results showed that the surface roughness of the modified biochar increased to different degrees with increases in specific surface area and pore volume, with the NaOH modified biochar showing the most significant increases from 4.96 m2·g-1 to 60.79 m2·g-1, and from 0.02 cm3·g-1 to 0.12 cm3·g-1, respectively. The pore diameter changed in the opposite direction. The absorption peaks of the functional groups of the modified biochar were all changed, with K3PO4 modified biochar exhibiting the greatest degree of change. The addition of biochar significantly improved the soil pH value (P<0.05), and the pH value of the soil treated with K3PO4 modified biochar exhibited the largest increase. With an application of 20.5% K3PO4 modified biochar, the availability of Cu and Cd in the soil was significantly reduced, by 75.44% and 67.70%, respectively. The immobilization efficiency of Cu was much higher than that of Cd. The best immobilization efficiency of Cu and Cd in soil was achieved with K3PO4 modified biochar. With an addition of 2% K3PO4 modified biochar, the immobilization efficiency of Cu and Cd was 61.06% and 4.12%, respectively. In summary, K3PO4 modified biochar had a better immobilization effect on both Cu and Cd in compound contaminated soil.