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Oocyte meiotic maturation failure and chromosome abnormality is one of the main causes of infertility, abortion, and diseases. The mono-orientation of sister chromatids during the first meiosis is important for ensuring accurate chromosome segregation in oocytes. MEIKIN is a germ cell-specific protein that can regulate the mono-orientation of sister chromatids and the protection of the centromeric cohesin complex during meiosis I. Here we found that MEIKIN is a maternal protein that was highly expressed in mouse oocytes before the metaphase I (MI) stage, but became degraded by the MII stage and dramatically reduced after fertilization. Strikingly, MEIKIN underwent phosphorylation modification after germinal vesicle breakdown (GVBD), indicating its possible function in subsequent cellular event regulation. We further showed that MEIKIN phosphorylation was mediated by PLK1 at its carboxyl terminal region and its C-terminus was its key functional domain. To clarify the biological significance of meikin degradation during later stages of oocyte maturation, exogenous expression of MEIKIN was employed, which showed that suppression of MEIKIN degradation resulted in chromosome misalignment, cyclin B1 and Securin degradation failure, and MI arrest through a spindle assembly checkpoint (SAC)-independent mechanism. Exogenous expression of MEIKIN also inhibited metaphase II (MII) exit and early embryo development. These results indicate that proper MEIKIN expression level and its C-terminal phosphorylation by PLK1 are critical for regulating the metaphase-anaphase transition in meiotic oocyte. The findings of this study are important for understanding the regulation of chromosome segregation and the prevention meiotic abnormality.
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In the agricultural lands of China, polyethylene is the main component of microplastics ï¼MPsï¼, with characteristics such as small size, wide distribution, easy accumulation, and difficult degradation. Therefore, it may have an impact on the elemental cycling process of the soil. On the basis of reviewing the key literatures in the past few years, this study systematically analyzed and summarized the key factors and processes of the polyethylene microplastics ï¼PE-MPsï¼ affecting soil nitrogen transformation. On the one hand, PE-MPs directly affected the activities of microorganisms and key enzymes related to soil nitrogen transformation by enriching microorganisms, selecting colonized microbial populations, and releasing additives. On the other hand, PE-MPs had indirect impacts on the activities of microorganisms and key enzymes related to soil nitrogen transformation by affecting soil physicochemical properties of soil and changing the microenvironment for microbial growth. Moreover, phthalates, an important additive of the MPs, may be the key factor affecting soil nitrogen transformation in the short-term. Finally, we posed key scientific issues that should be further studied in order to provide scientific support for nitrogen nutrition regulation and ecological risk assessment of soils contaminated by PE-MPs.
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Microplásticos , Nitrógeno , Polietileno , Contaminantes del Suelo , Suelo , Contaminantes del Suelo/análisis , Suelo/química , Microbiología del Suelo , ChinaRESUMEN
We propose and experimentally demonstrate a large-range and seamless rate-adaptive free-space optical (FSO) scheme based on rate compatible modulation (RCM). It utilizes a mapping method through weighted summation, enabling an even increase of bit energy. This allows the system to seamlessly adjust the throughput. In addition, the handover mechanism based on rate check and acknowledgment signals ensures a wide coverage of signal-to-noise ratio (SNR) fluctuation. It is worth noting that this scheme does not require any changes to the mapping matrix and decoding algorithm, making it easier to implement in real-world systems. Simulation proves the superiority of the proposed approach in terms of coding rate coverage by applying a fixed mapping matrix compared to a traditional adaptive modulation and coding scheme. Experimental demonstration over a 50â m FSO link verifies that the SNR dynamic range of this scheme is >15â dB with a seamless rate adjustment between 6.7â Gb/s and 53.6â Gb/s and the operability of RCM is not limited by the time scale of turbulence, revealing huge potential for the massive connections in future smart cities.
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The central histaminergic system has a pivotal role in emotional regulation and psychiatric disorders, including anxiety, depression and schizophrenia. However, the effect of histamine on neuronal activity of the centrolateral amygdala (CeL), an essential node for fear and anxiety processing, remains unknown. Here, using immunostaining and whole-cell patch clamp recording combined with optogenetic manipulation of histaminergic terminals in CeL slices prepared from histidine decarboxylase (HDC)-Cre rats, we show that histamine selectively suppresses excitatory synaptic transmissions, including glutamatergic transmission from the basolateral amygdala, on both PKC-δ- and SOM-positive CeL neurons. The histamine-induced effect is mediated by H3 receptors expressed on VGLUT1-/VGLUT2-positive presynaptic terminals in CeL. Furthermore, optoactivation of histaminergic afferent terminals from the hypothalamic tuberomammillary nucleus (TMN) also significantly suppresses glutamatergic transmissions in CeL via H3 receptors. Histamine neither modulates inhibitory synaptic transmission by presynaptic H3 receptors nor directly excites CeL neurons by postsynaptic H1, H2 or H4 receptors. These results suggest that histaminergic afferent inputs and presynaptic H3 heteroreceptors may hold a critical position in balancing excitatory and inhibitory synaptic transmissions in CeL by selective modulation of glutamatergic drive, which may not only account for the pathophysiology of psychiatric disorders but also provide potential psychotherapeutic targets. KEY POINTS: Histamine selectively suppresses the excitatory, rather than inhibitory, synaptic transmissions on both PKC-δ- and SOM-positive neurons in the centrolateral amygdala (CeL). H3 receptors expressed on VGLUT1- or VGLUT2-positive afferent terminals mediate the suppression of histamine on glutamatergic synaptic transmission in CeL. Optogenetic activation of hypothalamic tuberomammillary nucleus (TMN)-CeL histaminergic projections inhibits glutamatergic transmission in CeL via H3 receptors.
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Objective: To investigate the short-term effectiveness of unilateral biportal endoscopy (UBE) in treatment of lumbar lateral saphenous fossa combined with intervertebral foramina stenosis via contralateral sublaminar approach. Methods: A clinical data of 15 patients with lumbar lateral saphenous fossa combined with intervertebral foramina stenosis, who were admitted between September 2021 and December 2023 and met selective criteria, was retrospectively analyzed. There were 5 males and 10 females with an average age of 70.3 years (range, 46-83 years). Surgical segment was L 4, 5 in 12 cases and L 5, S 1 in 3 cases. The disease duration was 12-30 months (mean, 18.7 months). All patients were treated by UBE via contralateral sublaminar approach. The operation time, intraoperative blood loss, postoperative hospital stay, and the occurrence of complications were recorded. The visual analogue scale (VAS) score was used to evaluate the degree of lower back and leg pain before and after operation; the Japanese Orthopaedic Association (JOA) score and the Oswestry disability index (ODI) were used to evaluate the lumbar function; and the clinical outcome was evaluated using the MacNab criteria at 6 months after operation. Postoperative MRI and CT were taken to observe whether the lateral saphenous fossa and intervertebral foramen stenosis were removed or not, and the cross-sectional area of the spinal canal (CSA-SC), cross-sectional area of the intervertebral foramen (CSA-IVF), and cross-sectional area of the facet joint (CSA-FJ) were measured. Results: The operation time was 55-200 minutes (mean, 127.5 minutes); the intraoperative blood loss was 10-50 mL (mean, 27.3 mL); the length of postoperative hospital stay was 3-12 days (mean, 6.8 days). All patients were followed up 6-12 months (mean, 8.9 months). At 1 day, 1 month, 3 months, and 6 months after operation, the VAS scores of low back and leg pain and ODI scores after operation were significantly lower than preoperative scores and showed a gradual decrease with time; the JOA scores showed a gradual increase with time; the differences in the above indexes between different time points were significant ( P<0.05). The clinical outcome was rated as excellent in 10 cases, good in 4 cases, and poor in 1 case according to the MacNab criteria at 6 months after operation, with an excellent and good rate of 93.33%. Imaging review showed that the compression on the lateral saphenous fossa and intervertebral foramina had been significantly relieved, and the affected articular process joint was preserved to the maximum extent; the CSA-SC and CSA-IVF at 3 days after operation significantly increased compared to the preoperative values ( P<0.05), and the CSA-FJ significantly reduced ( P<0.05). Conclusion: The UBE via contralateral sublaminar approach can effectively reduce pressure in the lateral saphenous fossa and the intervertebral foramina of the same segment while preserving the bilateral articular process joints. The short-term effectiveness is good and it is expected to avoid fusion surgery caused by iatrogenic instability of the lumbar spine. However, further follow-up is needed to clarify the mid- and long-term effectiveness.
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Endoscopía , Vértebras Lumbares , Estenosis Espinal , Humanos , Masculino , Femenino , Estenosis Espinal/cirugía , Persona de Mediana Edad , Anciano , Vértebras Lumbares/cirugía , Endoscopía/métodos , Resultado del Tratamiento , Anciano de 80 o más Años , Descompresión Quirúrgica/métodos , Dimensión del Dolor , Dolor de la Región Lumbar/etiología , Dolor de la Región Lumbar/cirugíaRESUMEN
BACKGROUND: How to quickly read and interpret intraoperative ultrasound (IOUS) images of patients with degenerative cervical myelopathy (DCM) to obtain meaningful information? Few studies have systematically explored this topic. PURPOSE: To systematically and comprehensively explore the IOUS characteristics of patients with DCM. MATERIALS AND METHODS: This single-center study retrospectively included patients with DCM who underwent French-door laminoplasty (FDL) with IOUS guidance from October 2019 to March 2022. One-way ANOVA and Pearson's /Spearman's correlation analysis were used to analyze the correlations between the cross-sectional area of the spinal cord (SC) and individual characteristics; the relationships between the morphology, echogenicity, pulsation, decompression statuses, compression types of SC, location of the spinal cord central echo complex (SCCEC) and the disease severity (the preoperative Japanese Orthopedic Association score, preJOA score); the difference of the spinal cord pulsation amplitude(SCPA) and the SCCEC forward movement rate (FMR) between the compressed areas(CAs) and the non-compressed areas (NCAs). RESULTS: A total of 38 patients were successfully enrolled (30 males and 8 females), and the mean age was 57.05 ± 10.29 (27-75) years. The cross-sectional area of the SC was negatively correlated with age (r = - 0.441, p = 0.006). The preJOA score was significantly lower in the heterogeneous group than in the homogeneous group (P < 0.05, p = 0.005). The hyperechoic area (HEA) was negatively while the SCCEC FMR was positively correlated with the preJOA score (r = - 0.334, p = 0.020; r = 0.286, p = 0.041). The SCCEC FMR and SCPA in CAs were significantly greater than those in NCAs (p < 0.05, p = 0.007; P < 0.001, P = 0.000). CONCLUSION: The cross-sectional area of the SC decreases with age in adults. More changes in intramedullary echogenicity and less moving forward of the SCCEC often indicate poor SC status, and the SCCEC FMR and SCPA are more pronounced in CAs.
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Vértebras Cervicales , Laminoplastia , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Vértebras Cervicales/cirugía , Vértebras Cervicales/diagnóstico por imagen , Adulto , Laminoplastia/métodos , Enfermedades de la Médula Espinal/cirugía , Enfermedades de la Médula Espinal/diagnóstico por imagen , Ultrasonografía , Compresión de la Médula Espinal/cirugía , Compresión de la Médula Espinal/diagnóstico por imagenRESUMEN
Objective: To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons (PAHs) during critical brain development and explore their potential link with the intestinal microbiota. Methods: Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs (OH-PAHs) in 36-month-old children. Subsequently, 37 children were categorized into low- and high-exposure groups based on the sum of the ten OH-PAHs. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples. Furthermore, fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results: The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group (variable importance for projection > 1, P < 0.05). Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene, fluorine, and phenanthrene ( r = 0.336-0.531). The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states, including amino acid, lipid, and nucleotide metabolism. Additionally, these distinct metabolites were significantly associated with specific intestinal flora abundances ( r = 0.34-0.55), which were mainly involved in neurodevelopment. Conclusion: Higher PAH exposure in young children affected metabolic homeostasis, particularly that of certain gut microbiota-derived metabolites. Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.
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Microbioma Gastrointestinal , Hidrocarburos Policíclicos Aromáticos , Humanos , Hidrocarburos Policíclicos Aromáticos/metabolismo , Hidrocarburos Policíclicos Aromáticos/toxicidad , Hidrocarburos Policíclicos Aromáticos/orina , Masculino , Preescolar , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Exposición a Riesgos Ambientales/efectos adversos , Contaminantes Ambientales/toxicidad , Contaminantes Ambientales/metabolismo , Metabolómica , Metaboloma/efectos de los fármacosRESUMEN
Renal aging and the subsequent rise in kidney-related diseases are attributed to senescence in renal tubular epithelial cells (RTECs). Our study revealed that the abnormal expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), a reader of RNA N6-methyladenosine, is critically involved in cisplatin-induced renal tubular senescence. In cisplatin-induced senescence of RTECs, the promoter activity and transcription of IGF2BP3 is markedly suppressed. It was due to the down regulation of MYC proto-oncogene (MYC), which regulates IGF2BP3 transcription by binding to the putative site at 1852-1863 of the IGF2BP3 promoter. Overexpression of IGF2BP3 ameliorated cisplatin-induced renal tubular senescence in vitro. Mechanistic studies revealed that IGF2BP3 inhibits cellular senescence in RTECs by enhancing cyclin-dependent kinase 6 (CDK6) mRNA stability and increasing its expression. The inhibition effect of IGF2BP3 on tubular senescence is partially reversed by the knockdown of CDK6. Further, IGF2BP3 recruits nuclear cap binding protein subunit 1 (NCBP1) and inhibits CDK6 mRNA decay, by recognizing m6A modification. Specifically, IGF2BP3 recognizes m6A motif "GGACU" at nucleotides 110-114 in the 5' untranslated region (UTR) field of CDK6 mRNA. The involvement of IGF2BP3/CDK6 in alleviating tubular senescence was confirmed in a cisplatin-induced acute kidney injury (AKI)-to-chronic kidney disease (CKD) model. Clinical data also suggests an age-related decrease in IGF2BP3 and CDK6 levels in renal tissue or serum samples from patients. These findings suggest that IGF2BP3/CDK6 may be a promising target in cisplatin-induced tubular senescence and renal failure.
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Bone marrow mesenchymal stem cells (BMSCs) possess the potential to differentiate into cartilage cells. Long noncoding RNA (lncRNAs) urothelial carcinoma associated 1 (UCA1) has been confirmed to improve the chondrogenic differentiation of marrow mesenchymal stem cells (MSCs). Herein, we further investigated the effects and underlying mechanisms of these processes. The expression of UCA1 was positively associated with chondrogenic differentiation and the knockdown of UCA1 has been shown to attenuate the expression of chondrogenic markers. RNA pull-down assay and RNA immunoprecipitation showed that UCA1 could directly bind to PARP1 protein. UCA1 could improve PARP1 protein via facilitating USP9X-mediated PARP1 deubiquitination. Then these processes stimulated the NF-κB signaling pathway. In addition, PARP1 was declined in UCA1 knockdown cells, and silencing of PARP1 could diminish the increasing effects of UCA1 on the chondrogenic differentiation from MSCs and signaling pathway activation. Collectively, these outcomes suggest that UCA1 could act as a mediator of PARP1 protein ubiquitination and develop the chondrogenic differentiation of MSCs.
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Diferenciación Celular , Condrogénesis , Células Madre Mesenquimatosas , Poli(ADP-Ribosa) Polimerasa-1 , ARN Largo no Codificante , Ubiquitinación , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Humanos , Diferenciación Celular/genética , Condrogénesis/genética , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Poli(ADP-Ribosa) Polimerasa-1/genética , Transducción de Señal , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/citología , FN-kappa B/metabolismoRESUMEN
OBJECTIVE: The optimal methods for removing polyps remain controversial especially for polyps ≤10mm. We aim to combine the latest evidence to evaluate and compare the effectiveness and safety of cold snare polypectomy (CSP) and hot snare polypectomy (HSP) in the removal of colorectal polyps ≤10mm in size. METHODS: We performed an extensive search across multiple databases, including PubMed, Embase, Cochrane, and Web of Science, with the search period ending in April 2023 for randomized controlled trials comparing the effectiveness and/or safety of CSP and HSP for the removal of ≤10mm colorectal polyps.The final outcomes included complete resection rate, operation time, and postoperative adverse events (including immediate bleeding, delayed bleeding, and perforation) rates. RESULTS: A total of 14 eligible randomized controlled trials were included, involving 7,460 patients and 15,829 polyps. The incidence of immediate bleeding was observed to be more prevalent in CSP in contrast to HSP, and the disparity was statistically notable (OR=2.18, 95% CI: 1.43-3.30, I2=36%, P=0.0003). The incidence of delayed bleeding was observed to be lower in CSP in contrast to HSP, and this difference was statistically significant (OR=0.30, 95% CI: 0.15-0.58, I2=0%, P=0.0003). Procedure time: both the total colonoscopy time and specific polypectomy time were shorter in CSP than in HSP (MD=-5.92, 95% CI: -9.70 to -2.14, I2=96%, P=0.002; MD=-0.56, 95% CI: -0.91 to -0.20, I2=77%, P=0.002). There were no statistically significant differences in complete resection and the polyp retrieval rate between CSP and HSP. CONCLUSION: CSP is as effective and safe as HSP for ≤10mm colorectal polyps, while effectively reducing the risk of delayed bleeding and shortening the procedure time.
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Cardioembolic stroke, characterized by severe illness, poor prognosis, and high recurrence rate, is one of the important causes of ischemic stroke. In the field of genetic research, numerous genes associated with cardioembolic stroke have been identified, and their potential in predicting disease risk and evaluating risk factors has been progressively explored. Here, we provide an overview of the latest advancements in genetics for cardioembolic stroke, including genome-wide association studies, copy number variation studies, whole-genome sequencing studies. Furthermore, we also summarize the application of genetic datasets in polygenic risk score and Mendelian randomization. The aim of this overview is to provide insights and references from multiple perspectives for future investigations on the genetic information for cardioembolic stroke.
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Variaciones en el Número de Copia de ADN , Accidente Cerebrovascular Embólico , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Accidente Cerebrovascular Embólico/genética , Accidente Cerebrovascular Embólico/etiología , Factores de RiesgoRESUMEN
Objective: To compare the effectiveness of unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF) and endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) in the treatment of single-segment degenerative lumbar spinal stenosis with lumbar spondylolisthesis. Methods: Between November 2019 and May 2023, a total of 81 patients with single-segment degenerative lumbar spinal stenosis with lumbar spondylolisthesis who met the selection criteria were enrolled. They were randomly divided into UBE-TLIF group (39 cases) and Endo-TLIF group (42 cases). There was no significant difference in baseline data between the two groups ( P>0.05), including gender, age, body mass index, surgical segment, and preoperative visual analogue scale (VAS) scores for low back and leg pain, Oswestry Disability Index (ODI), and serum markers including creatine kinase (CK) and C reactive protein (CRP). Total blood loss (TBL), intraoperative blood loss, hidden blood loss (HBL), postoperative drainage volume, and operation time were recorded and compared between the two groups. Serum markers (CK, CRP) levels were compared between the two groups at 1 day before operation and 1, 3, and 5 days after operation. Furthermore, the VAS scores for low back and leg pain, and ODI at 1 day before operation and 1 day, 3 months, 6 months, and 12 months after operation, and intervertebral fusion rate at 12 months after operation were compared between the two groups. Results: All surgeries were completed successfully without occurrence of incision infection, vascular or nerve injury, epidural hematoma, dural tear, or postoperative paraplegia. The operation time in UBE-TLIF group was significantly shorter than that in Endo-TLIF group, but the intraoperative blood loss, TBL, and HBL in UBE-TLIF group were significantly more than those in Endo-TLIF group ( P<0.05). There was no significant difference in postoperative drainage volume between the two groups ( P>0.05). The levels of CK at 1 day and 3 days after operation and CRP at 1, 3, and 5 days after operation in UBE-TLIF group were slightly higher than those in the Endo-TLIF group ( P<0.05), while there was no significant difference in the levels of CK and CPR between the two groups at other time points ( P>0.05). All patients were followed up 12 months. VAS score of low back and leg pain and ODI at each time point after operation significantly improved when compared with those before operation in the two groups ( P<0.05); there was no significant difference in VAS score of low back and leg pain and ODI between the two groups at each time point after operation ( P>0.05). There was no significant difference in the intervertebral fusion rate between the two groups at 12 months after operation ( P>0.05). Conclusion: UBE-TLIF and Endo-TLIF are both effective methods for treating degenerative lumbar spinal stenosis with lumbar spondylolisthesis. However, compared to Endo-TLIF, UBE-TLIF requires further improvement in minimally invasive techniques to reduce tissue trauma and blood loss.
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Endoscopía , Vértebras Lumbares , Fusión Vertebral , Estenosis Espinal , Espondilolistesis , Humanos , Fusión Vertebral/métodos , Espondilolistesis/cirugía , Estenosis Espinal/cirugía , Vértebras Lumbares/cirugía , Endoscopía/métodos , Estudios Prospectivos , Resultado del Tratamiento , Masculino , Femenino , Complicaciones Posoperatorias , Persona de Mediana EdadRESUMEN
Myocardial ischemia-reperfusion (I/R) injury stands out among cardiovascular diseases, and current treatments are considered unsatisfactory. For cardiomyocytes (CMs) in ischemic tissues, the upregulation of Limb-bud and Heart (LBH) and αB-crystallin (CRYAB) and their subsequent downregulation in the context of cardiac fibrosis have been verified in our previous research. Here, we focused on the effects and mechanisms of activated LBH-CRYAB signaling on damaged CMs during I/R injury, and confirmed the occurrence of mitochondrial apoptosis and ferroptosis during I/R injury. The application of inhibitors, ectopic expression vectors, and knockout mouse models uniformly verified the role of LBH in alleviating both apoptosis and ferroptosis of CMs. p53 was identified as a mutual downstream effector for both LBH-CRYAB-modulated apoptosis and ferroptosis inhibition. In mouse models, LBH overexpression was confirmed to exert enhanced cardiac protection against I/R-induced apoptosis and ferroptosis, suggesting that LBH could serve as a promising target for the development of I/R therapy.
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INTRODUCTION: It is estimated that 90% of hyperuricemia cases are attributed to the inability to excrete uric acid (UA). The two main organs in charge of excreting UA are the kidney (70%) and intestine (30%). Previous studies have reported that punicalagin (PU) could protect against kidney and intestinal damages, which makes it a potential candidate for alleviating hyperuricemia. However, the effects and deeper action mechanisms of PU for managing hyperuricemia are still unknown. OBJECTIVE: To investigate the effect and action mechanisms of PU for ameliorating hyperuricemia. METHODS: The effects and action mechanisms of PU on hyperuricemia were assessed using a hyperuricemia mice model. Phenotypic parameters, metabolomics analysis, and 16S rRNA sequencing were applied to explore the effect and fundamental action mechanisms inside the kidney and intestine of PU for improving hyperuricemia. RESULTS: PU administration significantly decreased elevated serum uric acid (SUA) levels in hyperuricemia mice, and effectively alleviated the kidney and intestinal damage caused by hyperuricemia. In the kidney, PU down-regulated the expression of UA resorption protein URAT1 and GLUT9, while up-regulating the expression of UA excretion protein ABCG2 and OAT1 as mediated via the activation of MAKP/NF-κB in hyperuricemia mice. Additionally, PU attenuated renal glycometabolism disorder, which contributed to improving kidney dysfunction and inflammation. Similarly, PU increased UA excretion protein expression via inhibiting MAKP/NF-κB activation in the intestine of hyperuricemia mice. Furthermore, PU restored gut microbiota dysbiosis in hyperuricemia mice. CONCLUSION: This research revealed the ameliorating impacts of PU on hyperuricemia by restoring kidney and intestine damage in hyperuricemia mice, and to be considered for the development of nutraceuticals used as UA-lowering agent.
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The trivalent phosphine-catalyzed [4+1] spiro-annulation reaction of allenyl imide and activated methylene cyclocompounds has been developed for the construction of various spiro-2-cyclopenten-1-ones. Oxindoles, 3-isochromanones, and 2-indanones are selected as 1C synthons to capture the in situ-generated bis-electrophilic α,ß-unsaturated ketenyl phosphonium intermediate, affording the corresponding monospiro- and bispiro-cyclopentenones in good to excellent yields (≤91%) under mild conditions. The primary attempt at asymmetric catalysis using monophosphine (R)-SITCP provides promising enantioselectivity (45% ee). A plausible reaction mechanism is also proposed.
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Oleanolic acid and its derivatives are widely used in the pharmaceutical, agricultural, cosmetic and food industries. Previous studies have shown that oleanolic acid production levels in engineered cell factories are low, which is why oleanolic acid is still widely extracted from traditional medicinal plants. To construct a highly efficient oleanolic acid production strain, rate-limiting steps were regulated by inducible promoters and the expression of key genes in the oleanolic acid synthetic pathway was enhanced. Subsequently, precursor pool expansion, pathway refactoring and diploid construction were considered to harmonize cell growth and oleanolic acid production. The multi-strategy combination promoted oleanolic acid production of up to 4.07 g/L in a 100 L bioreactor, which was the highest level reported.
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Ácido Oleanólico , Saccharomyces cerevisiae , Ácido Oleanólico/biosíntesis , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Reactores Biológicos , Ingeniería Metabólica/métodos , Ingeniería Genética/métodos , Regiones Promotoras GenéticasRESUMEN
Esophageal carcinoma (ESCA) is an aggressive solid tumor. The 5-year survival rate for patients with ESCA is estimated to be less than 20%, mainly due to tumor invasion and metastasis. Therefore, it is urgent to improve early diagnostic tools and effective treatments for ESCA patients. Tumor microenvironment (TME) enhances the ability of tumor cells to proliferate, migrate, and escape from the immune system, thus promoting the occurrence and development of tumor. TME contains chemokines. Chemokines consist of four major families, which are mainly composed of CC and CXC families. The main purpose of this review is to understand the CC and CXC chemokines and their receptors in ESCA, to improve the understanding of tumorigenesis of ESCA and determine new biomarkers for the diagnosis and prognosis of ESCA. We reviewed the literature on CC and CXC chemokines and their receptors in ESCA identified by PubMed database. This article introduces the general structures and functions of CC, CXC chemokines and their receptors in TME, as well as their roles in the progress of ESCA. Chemokines are involved in the development of ESCA, such as cancer cell invasion, metastasis, angiogenesis, and radioresistance, and are key determinants of disease progression, which have a great impact on patient prognosis and treatment response. In addition, a full understanding of their mechanism of action is essential to further verify that these chemokines and their receptors may serve as biomarkers or therapeutic targets of ESCA.
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Quimiocinas , Neoplasias Esofágicas , Microambiente Tumoral , Humanos , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/inmunología , Quimiocinas/metabolismo , Receptores de Quimiocina/metabolismo , Biomarcadores de Tumor/metabolismo , PronósticoRESUMEN
Prostaglandin E2 (PGE2) is an important lipid molecule derived from arachidonic acid, which regulates a variety of physiological and pathological activities. Based on the inhibition of inflammatory PGE2 production, non-steroidal anti-inflammatory drugs (NSAIDs) are considered as the most commonly used drugs to treat inflammatory diseases and to relieve fever and pain symptoms. PGE2 mediates its functions via four different G protein-coupled receptors, named EP1-EP4. Though the limited distribution and low PGE2 affinity of EP1, it plays important roles in the maintenance of many physiological functions and homeostasis. Moreover, EP1 is widely involved in the inflammatory response, pain perception and multisystem pathological function regulation. In this review, we will briefly summarize the recent advances on the physiological and pathophysiological function of EP1 and its targeted drugs development.
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Dinoprostona , Dolor , Humanos , Ácido Araquidónico , HomeostasisRESUMEN
Physical exercise is known to reduce anxiety, but the underlying brain mechanisms remain unclear. Here, we explore a hypothalamo-cerebello-amygdalar circuit that may mediate motor-dependent alleviation of anxiety. This three-neuron loop, in which the cerebellar dentate nucleus takes center stage, bridges the motor system with the emotional system. Subjecting animals to a constant rotarod engages glutamatergic cerebellar dentate neurons that drive PKCδ+ amygdalar neurons to elicit an anxiolytic effect. Moreover, challenging animals on an accelerated rather than a constant rotarod engages hypothalamic neurons that provide a superimposed anxiolytic effect via an orexinergic projection to the dentate neurons that activate the amygdala. Our findings reveal a cerebello-limbic pathway that may contribute to motor-triggered alleviation of anxiety and that may be optimally exploited during challenging physical exercise.
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Ansiolíticos , Animales , Ansiedad/metabolismo , Hipotálamo , Cerebelo , Trastornos de AnsiedadRESUMEN
Turbulent energy dissipation is a fundamental process in plasma physics that has not been settled. It is generally believed that the turbulent energy is dissipated at electron scales leading to electron energization in magnetized plasmas. Here, we propose a micro accelerator which could transform electrons from isotropic distribution to trapped, and then to stream (Strahl) distribution. From the MMS observations of an electron-scale coherent structure in the dayside magnetosheath, we identify an electron flux enhancement region in this structure collocated with an increase of magnetic field strength, which is also closely associated with a non-zero parallel electric field. We propose a trapping model considering a field-aligned electric potential together with the mirror force. The results are consistent with the observed electron fluxes from ~50 eV to ~200 eV. It further demonstrates that bidirectional electron jets can be formed by the hourglass-like magnetic configuration of the structure.