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Neutralizing antibodies (nAbs) are important assets to fight COVID-19, but most existing nAbs lose the activities against Omicron subvariants. Here, we report a human monoclonal antibody (Ab08) isolated from a convalescent patient infected with the prototype strain (Wuhan-Hu-1). Ab08 binds to the receptor-binding domain (RBD) with pico-molar affinity (230 pM), effectively neutralizes SARS-CoV-2 and variants of concern (VOCs) including Alpha, Beta, Gamma, Mu, Omicron BA.1 and BA.2, and to a lesser extent for Delta and Omicron BA.4/BA.5 which bear the L452R mutation. Of medical importance, Ab08 shows therapeutic efficacy in SARS-CoV-2-infected hACE2 mice. X-ray crystallography of the Ab08-RBD complex reveals an antibody footprint largely in the ß-strand core and away from the ACE2-binding motif. Negative staining electron-microscopy suggests a neutralizing mechanism through which Ab08 destructs the Spike trimer. Together, our work identifies a nAb with therapeutic potential for COVID-19.
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Anticorpos Monoclonais , COVID-19 , SARS-CoV-2 , Animais , Humanos , Camundongos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Glicoproteína da Espícula de Coronavírus/genéticaRESUMO
Architected materials can actively respond to external stimuli-such as mechanical forces, hydration and magnetic fields-by changing their geometries and thereby achieve novel functionalities. Such transformations are usually binary and volatile because they toggle between 'on' and 'off' states and require persistent external stimuli. Here we develop three-dimensional silicon-coated tetragonal microlattices that transform into sinusoidal patterns via cooperative beam buckling in response to an electrochemically driven silicon-lithium alloying reaction. In situ microscopy reveals a controllable, non-volatile and reversible structural transformation that forms multiple ordered buckling domains separated by distorted domain boundaries. We investigate the mechanical dynamics of individual buckling beams, cooperative coupling among neighbouring beams, and lithiation-rate-dependent distributions of domain sizes through chemo-mechanical modelling and statistical mechanics analysis. Our results highlight the critical role of defects and energy fluctuations in the dynamic response of architected materials. We further demonstrate that domain boundaries can be programmed to form particular patterns by pre-designing artificial defects, and that a variety of reconfigurational degrees of freedom can be achieved through micro-architecture design. This framework enables the design, fabrication, modelling, behaviour prediction and programming of electrochemically reconfigurable architected materials, and could open the way to beyond-intercalation battery electrodes, tunable phononic crystals and bio-implantable devices.
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The alteration of neural interactions across different cerebral perfusion states remains unclear. This study aimed to fulfill this gap by examining the longitudinal brain dynamic information interactions before and after cerebral reperfusion. Electroencephalogram in eyes-closed state at baseline and postoperative 7-d and 3-month follow-ups (moyamoya disease: 20, health controls: 23) were recorded. Dynamic network analyses were focused on the features and networks of electroencephalogram microstates across different microstates and perfusion states. Considering the microstate features, the parameters were disturbed of microstate B, C, and D but preserved of microstate A. The transition probabilities of microstates A-B and B-D were increased to play a complementary role across different perfusion states. Moreover, the microstate variability was decreased, but was significantly improved after cerebral reperfusion. Regarding microstate networks, the functional connectivity strengths were declined, mainly within frontal, parietal, and occipital lobes and between parietal and occipital lobes in different perfusion states, but were ameliorated after cerebral reperfusion. This study elucidates how dynamic interaction patterns of brain neurons change after cerebral reperfusion, which allows for the observation of brain network transitions across various perfusion states in a live clinical setting through direct intervention.
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Encéfalo , Eletroencefalografia , Encéfalo/fisiologia , Mapeamento Encefálico , Perfusão , Circulação CerebrovascularRESUMO
A high concentration of sodium (Na+) is the primary stressor for plants in high salinity environments. The Salt Overly Sensitive (SOS) pathway is one of the best-studied signal transduction pathways, which confers plants the ability to export too much Na+ out of the cells or translocate the cytoplasmic Na+ into the vacuole. In this study, the Salt Overly Sensitive3 (MpSOS3) gene from Pongamia (Millettia pinnata Syn. Pongamia pinnata), a semi-mangrove, was isolated and characterized. The MpSOS3 protein has canonical EF-hand motifs conserved in other calcium-binding proteins and an N-myristoylation signature sequence. The MpSOS3 gene was significantly induced by salt stress, especially in Pongamia roots. Expression of the wild-type MpSOS3 but not the mutated nonmyristoylated MpSOS3-G2A could rescue the salt-hypersensitive phenotype of the Arabidopsis sos3-1 mutant, which suggested the N-myristoylation signature sequence of MpSOS3 was required for MpSOS3 function in plant salt tolerance. Heterologous expression of MpSOS3 in Arabidopsis accumulated less H2O2, superoxide anion radical (O2-), and malondialdehyde (MDA) than wild-type plants, which enhanced the salt tolerance of transgenic Arabidopsis plants. Under salt stress, MpSOS3 transgenic plants accumulated a lower content of Na+ and a higher content of K+ than wild-type plants, which maintained a better K+/Na+ ratio in transgenic plants. Moreover, no development and growth discrepancies were observed in the MpSOS3 heterologous overexpression plants compared to wild-type plants. Our results demonstrated that the MpSOS3 pathway confers a conservative salt-tolerant role and provided a foundation for further study of the SOS pathway in Pongamia.
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Arabidopsis , Clonagem Molecular , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Plantas Geneticamente Modificadas , Tolerância ao Sal , Plantas Tolerantes a Sal , Plantas Tolerantes a Sal/genética , Plantas Tolerantes a Sal/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Tolerância ao Sal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Cloreto de Sódio/farmacologia , Sequência de Aminoácidos , Filogenia , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Estresse Salino/genética , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismoRESUMO
Subarachnoid hemorrhage (SAH) is a form of severe acute stroke with very high mortality and disability rates. Early brain injury (EBI) and delayed cerebral ischemia (DCI) contribute to the poor prognosis of patients with SAH. Currently, some researchers have started to focus on changes in amino acid metabolism that occur in brain tissues after SAH. Taurine is a sulfur-containing amino acid that is semi-essential in animals, and it plays important roles in various processes, such as neurodevelopment, osmotic pressure regulation, and membrane stabilization. In acute stroke, such as cerebral hemorrhage, taurine plays a neuroprotective role. However, the role of taurine after subarachnoid hemorrhage has rarely been reported. In the present study, we established a mouse model of SAH. We found that taurine administration effectively improved the sensorimotor function of these mice. In addition, taurine treatment alleviated sensorimotor neuron damage and reduced the proportion of apoptotic cells. Furthermore, taurine treatment enhanced the polarization of astrocytes toward the neuroprotective phenotype while inhibiting their polarization toward the neurotoxic phenotype. This study is the first to reveal the relationship between taurine and astrocyte polarization and may provide a new strategy for SAH research and clinical treatment.
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Acidente Vascular Cerebral , Hemorragia Subaracnóidea , Humanos , Animais , Camundongos , Hemorragia Subaracnóidea/tratamento farmacológico , Taurina/farmacologia , Astrócitos , Apoptose , AminoácidosRESUMO
OBJECTIVES: To compare the efficiency and safety of a novel flexible ureteral access sheath (f-UAS) and traditional ureteral access sheath (UAS) during retrograde intrarenal surgery (RIRS). PATIENTS AND METHODS: Between January 2022 and September 2022, a total of 152 consecutive cases with renal stones underwent RIRS with the f-UAS. Their outcomes were compared with those of another 152 consecutive cases undergoing RIRS with traditional UAS using a 1:1 scenario matched-pair analysis, with matching parameters including age and stone size. The f-UAS is a novel UAS with a 10-cm-long tube at the tip that can follow the bends of flexible ureteroscope (f-URS). RESULTS: Baseline characteristics were found to be similar between the two groups. The f-UAS group demonstrated significantly higher SFR (76.3% vs. 7.2%; P < 0.001) at 1 day postoperatively and a higher clearance rate of stone volume (98.11% vs. 91.78%; P < 0.001). The f-UAS group also had lower total complications rate (9.9% vs. 22.4%; P = 0.003), lower incidence of fever (5.9% vs 11.9%; P = 0.001), shorter operative times (56.5 min vs. 59.9 min; P = 0.047), and lower usage rate of baskets (17.1% vs. 100%; P < 0.001). There was no significant difference in SFR at 1 month postoperatively (P = 0.627) and in the length of postoperative hospital stay between the two groups (P = 0.225). CONCLUSION: Compared to the traditional UAS during RIRS, the f-UAS showed several advantages, including higher SFR at 1 day postoperatively, shorter operative times, lower incidence of complications, and less use of basket.
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Cálculos Renais , Ureter , Humanos , Masculino , Ureter/cirurgia , Febre , Prepúcio do Pênis , Cálculos Renais/cirurgia , Tempo de InternaçãoRESUMO
Pertechnetate (99TcO4-), a physiologically toxic radioactive anion, is of great concern due to its high mobility in environmental contamination remediation. Although the soluble oxyanion can be photoreduced to sparingly soluble TcO2·nH2O, its effective removal from a strongly acidic aqueous solution remains a challenge. Here, we found that low-crystalline nitrogen-doped titanium oxide (N-TiO2, 0.6 g L-1) could effectively uptake perrhenate (ReO4-, 10 mg L-1, a nonradioactive surrogate for TcO4-) with 50.8% during 360 min under simulated sunlight irradiation at pH 1.0, but P25 and anatase could not. The nitrogen active center formed by trace nitrogen doping in N-TiO2 can promote the separation and transfer of photogenerated carriers. The positive valence band value of N-TiO2 is slightly higher than those of P25 and anatase, which means that the photogenerated holes have a stronger oxidizability. These holes are involved in the formation of strong reducing â¢CO2- radicals from formic acid oxidation. The active radicals convert ReO4- to Re(VI), which is subsequently disproportionated to Re(IV) and Re(VII). Effective photocatalytic reduction/removal of Re(VII)/Tc(VII) is performed on the material, which may be considered a potential and convenient strategy for technetium decontamination and extraction in a strongly acidic aqueous solution.
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Titânio , Catálise , Titânio/química , Oxirredução , Rênio/química , Água/química , Concentração de Íons de Hidrogênio , SoluçõesRESUMO
OBJECTIVES: Prolonged mechanical ventilation (PMV) is a common complication following cardiac surgery linked to unfavorable patient prognosis and increased mortality. This study aimed to search for the factors associated with the occurrence of PMV after valve surgery and to develop a risk prediction model. METHODS: The patient cohort was divided into two groups based on the presence or absence of PMV post-surgery. Comprehensive preoperative and intraoperative clinical data were collected. Univariate and multivariate logistic regression analyses were employed to identify risk factors contributing to the incidence of PMV. Based on the logistic regression results, a clinical nomogram was developed. RESULTS: The study included 550 patients who underwent valve surgery, among whom 62 (11.27%) developed PMV. Multivariate logistic regression analysis revealed that age (odds ratio [OR] = 1.082, 95% confidence interval [CI] = 1.042-1.125; P < 0.000), current smokers (OR = 1.953, 95% CI = 1.007-3.787; P = 0.047), left atrial internal diameter index (OR = 1.04, 95% CI = 1.002-1.081; P = 0.041), red blood cell count (OR = 0.49, 95% CI = 0.275-0.876; P = 0.016), and aortic clamping time (OR = 1.031, 95% CI = 1.005-1.057; P < 0.017) independently influenced the occurrence of PMV. A nomogram was constructed based on these factors. In addition, a receiver operating characteristic (ROC) curve was plotted, with an area under the curve (AUC) of 0.782 and an accuracy of 0.884. CONCLUSION: Age, current smokers, left atrial diameter index, red blood cell count, and aortic clamping time are independent risk factors for PMV in patients undergoing valve surgery. Furthermore, the nomogram based on these factors demonstrates the potential for predicting the risk of PMV in patients following valve surgery.
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Nomogramas , Valor Preditivo dos Testes , Respiração Artificial , Humanos , Fatores de Risco , Masculino , Feminino , Pessoa de Meia-Idade , Respiração Artificial/efeitos adversos , Fatores de Tempo , Medição de Risco , Idoso , Estudos Retrospectivos , Resultado do Tratamento , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Técnicas de Apoio para a Decisão , Adulto , Implante de Prótese de Valva Cardíaca/efeitos adversos , Valvas Cardíacas/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Fatores EtáriosRESUMO
Extracellular regulated protein kinases 1/2 (ERK1/2) are key members of multiple signaling pathways, including the ErbB axis. Ectopic ERK1/2 activation contributes to various types of cancer, especially drug resistance to inhibitors of RTK, RAF and MEK, and specific ERK1/2 inhibitors are scarce. In this study, we identified a potential novel covalent ERK inhibitor, Laxiflorin B, which is a herbal compound with anticancer activity. However, Laxiflorin B is present at low levels in herbs; therefore, we adopted a semi-synthetic process for the efficient production of Laxiflorin B to improve the yield. Laxiflorin B induced mitochondria-mediated apoptosis via BAD activation in non-small-cell lung cancer (NSCLC) cells, especially in EGFR mutant subtypes. Transcriptomic analysis suggested that Laxiflorin B inhibits amphiregulin (AREG) and epiregulin (EREG) expression through ERK inhibition, and suppressed the activation of their receptors, ErbBs, via a positive feedback loop. Moreover, mass spectrometry analysis combined with computer simulation revealed that Laxiflorin B binds covalently to Cys-183 in the ATP-binding pocket of ERK1 via the D-ring, and Cys-178 of ERK1 through non-inhibitory binding of the A-ring. In a NSCLC tumor xenograft model in nude mice, Laxiflorin B also exhibited strong tumor suppressive effects with low toxicity and AREG and EREG were identified as biomarkers of Laxiflorin B efficacy. Finally, Laxiflorin B-4, a C-6 analog of Laxiflorin B, exhibited higher binding affinity for ERK1/2 and stronger tumor suppression. These findings provide a new approach to tumor inhibition using natural anticancer compounds.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Camundongos , Animais , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Sistema de Sinalização das MAP Quinases , Camundongos Nus , Simulação por Computador , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Mutação , Linhagem Celular TumoralRESUMO
The potential causal association between dyslipidemia and brain structures remains unclear. Therefore, this study aimed to investigate whether circulating lipids are causally associated with brain structure alterations using Mendelian randomization analysis. Genome-wide association study summary statistics of blood lipids and brain structures were obtained from publicly available databases. Inverse-variance weighted method was used as the primary method to assess causality. In addition, four additional Mendelian randomization methods (MR-Egger, weighted median, simple mode, and weighted mode) were applied to supplement inverse-variance weighted. Furthermore, Cochrane's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis were performed for sensitivity analyses. After Bonferroni corrections, two causal associations were finally identified: elevated non-high-density lipoprotein cholesterol level leads to higher average cortical thickness (ß = 0.0066 mm, 95% confidence interval: 0.0045-0.0087 mm, P = 0.001); and elevated high-density lipoprotein cholesterol level leads to higher inferior temporal surface area (ß = 18.6077 mm2, 95% confidence interval: 11.9835-25.2320 mm2, P = 0.005). Four additional Mendelian randomization methods indicated parallel results. Sensitivity tests demonstrated the stability. Overall, the present study showed causal relationships between several lipid profiles and specific brain structures, providing new insights into the link between dyslipidemia and neurological disorders.
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Dislipidemias , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Lipídeos , Encéfalo/diagnóstico por imagem , Colesterol , Dislipidemias/genéticaRESUMO
OBJECTIVES: Observational studies suggested a potential correlation between dietary intake and amyotrophic lateral sclerosis (ALS), but conflicting findings exist and causality remains unclear. Here, we performed a Mendelian randomization (MR) analysis to evaluate the causal impact of relative intake of (i) carbohydrate, (ii) fat, and (iii) protein on ALS risk. METHODS: The genome-wide association summary statistics of three dietary macronutrient intake traits and ALS were obtained. Initially, forward and reverse univariable MR (UVMR) analysis were conducted using the inverse variance weighted (IVW) method as the primary approach, supplemented by MR-Egger, weighted median, and maximum likelihood. Subsequently, multivariable MR (MVMR) analysis was performed to assess the independent causal effects of each dietary. Additionally, diverse sensitivity tests were conducted to evaluate the reliability of the MR analyses. RESULTS: The forward UVMR analysis conducted by IVW indicated that relative carbohydrate intake significantly increased ALS risk. Furthermore, results from three other MR methods paralleled those from IVW. However, the other two dietary intake traits did not have a causative impact on ALS risk. The reverse UVMR analysis indicated that ALS did not causatively influence the three dietary intake traits. The MVMR analysis showed that after adjusting for the effects of the other two dietary intake traits, relative carbohydrate intake independently and significantly increased ALS risk. Sensitivity tests indicated no significant heterogeneity or horizontal pleiotropy. DISCUSSION: MR analysis supported relative carbohydrate independently increasing ALS risk. Nevertheless, further validation of this finding in future large cohorts is required.Abbreviations: ALS: amyotrophic lateral sclerosis; CI: confidence interval; GWAS: genome-wide association study; IV: instrumental variable; IVW: iverse variance weighted; MR: Mendelian randomization; MVMR: multivariable Mendelian randomization; OR: odds ratio; RCT: randomized controlled trial; SNPs: single-nucleotide polymorphisms; UVMR: univariable Mendelian randomization.
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BACKGROUND: Circular RNAs (circRNAs) have been shown to be involved in tumorigenesis and progression. However, the role of circGLIS3 (hsa_circ_0002874) in prostate cancer (PCa) has yet not been reported. METHODS: Candidate circRNA were determined through comprehensive analysis of public datasets, PCa cell lines, and tissues data. A series of cellular functional assays, including CCK-8, colony formation, wound healing, and transwell assays were performed. Subsequently, RNA sequencing, RNA immunoprecipitation, methylated RNA immunoprecipitation, microRNA pulldown, luciferase reporter assay, and western blot were used to explore the underlying molecular mechanisms. Moreover, the xenograft tumor mouse model was established to elucidate the function of circGLIS3. RESULTS: CircGLIS3, derived from exon 2 of the parental GLIS3 gene, was identified as a novel oncogenic circRNA in PCa that was closely associated with the biochemical recurrence. Its expression levels were upregulated in PCa tissues and cell lines as well as enzalutamide high-resistant cells. The cellular functional assays revealed that circGLIS3 promoted PCa cell proliferation, migration, and invasion. METTL3-mediated N6-methyladenosine (m6A) modification maintained its upregulation by enhancing its stability. Mechanically, CircGLIS3 sponged miR-661 to upregulate MDM2, thus regulating the p53 signaling pathway to promote cell proliferation, migration, and invasion. Furthermore, in vitro and in vivo experiments, the knockdown of circGLIS3 improved the response of PCa cells to ARSI therapies such as enzalutamide. CONCLUSIONS: METTL3-mediated m6A modification of circGLIS3 regulates the p53 signaling pathway via the miR-661/MDM2 axis, thereby facilitating PCa progression. Meanwhile, this study unveils a promising potential target for ARSI therapy for PCa.
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Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Metiltransferases , Neoplasias da Próstata , RNA Circular , Masculino , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Animais , Metiltransferases/metabolismo , Metiltransferases/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Camundongos , Adenosina/análogos & derivados , Adenosina/metabolismo , Movimento Celular/genética , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Feniltioidantoína/farmacologia , Feniltioidantoína/análogos & derivados , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Resistencia a Medicamentos Antineoplásicos/genética , Camundongos Endogâmicos BALB C , Benzamidas , NitrilasRESUMO
BACKGROUND: Parkinson's disease (PD) is the second most prevalent degenerative disease globally. While observational studies have demonstrated a correlation between thyroid function and PD, the causal relationship between these two factors remains uncertain. METHODS: A bidirectional Mendelian randomization (MR) analysis was performed to explore the causal relationship between thyroid function (free thyroxine [FT4], thyroid-stimulating hormone [TSH], hyperthyroidism, and hypothyroidism) and PD. GWAS summary-level statistics of thyroid function and PD were obtained from publicly available GWAS databases. The inverse variance weighted method was the main MR approach to assess causal associations. In addition, two additional MR methods (MR-Egger regression and weighted median) were performed to supplement the IVW. Furthermore, various sensitivity tests were performed to verify the reliability of the MR findings: (i) Heterogeneity was examined by Cochrane's Q test. (ii) Horizontal pleiotropy was assessed by the MR-Egger intercept test and MR-PRESSO global test. (iii) The robustness of MR results was estimated using the leave-one-out method. RESULTS: Various MR results showed that FT4, TSH, hyperthyroidism, and hypothyroidism did not causally affect PD (P > 0.05). Likewise, PD did not causally affect FT4, TSH, hyperthyroidism, and hypothyroidism (P > 0.05). Cochrane's Q test indicated that MR analysis was not affected by significant heterogeneity (P > 0.05). MR-Egger intercept test and MR-PRESSO global test indicated that MR analysis was not affected by a remarkable horizontal pleiotropy (P > 0.05). The leave-one-out method demonstrated the stability of MR results. CONCLUSION: MR analysis did not support a causal relationship between thyroid function and PD.
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Hipertireoidismo , Hipotireoidismo , Doença de Parkinson , Humanos , Estudo de Associação Genômica Ampla , Hipertireoidismo/genética , Hipotireoidismo/genética , Análise da Randomização Mendeliana , Nonoxinol , Doença de Parkinson/genética , Reprodutibilidade dos Testes , TireotropinaRESUMO
BACKGROUND: Esketamine, recognized for its analgesic, sedative, and anti-inflammatory qualities, is integral in multimodal analgesia. However, the potential opioid-sparing effects of intravenous esketamine, along with its impact on inflammatory responses, and cognitive function during laparoscopic surgery, remain unexplored. METHODS: In this study, 90 patients scheduled for laparoscopic cholecystectomy were equally randomized into three groups: a normal saline control group (NS), a low-dose esketamine group (LS) and a high-dose esketamine group (HS). Subsequently, we monitored several parameters: hemodynamics, levels of stress and inflammatory responses, intraoperative doses of sufentanil, remifentanil, and propofol, and 24-hour postoperative sufentanil requirements. We also evaluated alterations in cognitive function, perioperative indicators, and potential adverse reactions among the three groups. RESULTS: Compared to their levels 5 minutes prior to anesthesia (T0) and 30 minutes post-operation (T4), the NS group exhibited a more significant decrease in Mean Arterial Pressure (MAP) and Heart Rate (HR) at various time intervals: 5 minutes after the skin incision (T1), 30 minutes post-incision (T2), and at the conclusion of the operation (T3), compared to the LS and HS groups(P < 0.05). Furthermore, the NS group exhibited a greater increase in levels of adrenaline (AD), noradrenaline (NE), endothelin (ET), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) at T1, T2, and T3, more so than the other two groups(P < 0.05). 24 hours after the surgery, patients in the LS group and HS group had significantly higher Montreal Cognitive Assessment (MoCA) scores than those in the NS group(P < 0.05). The LS and HS groups required lower doses of propofol, remifentanil, and sufentanil during surgery (P < 0.05), experienced shorter postoperative recovery times, and had lower incidences of nausea, vomiting, and respiratory depression compared to the NS group (P < 0.05). CONCLUSION: The administration of low-dose esketamine has been shown to be safe, effective, and dependable in the context of laparoscopic gallbladder surgery. It has the capacity to stabilize hemodynamic responses, ameliorate both stress and inflammatory reactions from surgery, and hastens anesthesia recovery. Furthermore, it fosters the restoration of postoperative cognitive function. Notably, when combined with nalbuphine, it exhibits opioid-sparing effects, reducing postoperative adverse outcomes. TRIAL REGISTRATION: The trial is registered with the China Clinical Trials Registry Registration Number: ChiCTR2300067596. Retrospectively registered (date of registration: 12/01/2023).
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Colecistectomia Laparoscópica , Ketamina , Propofol , Humanos , Analgésicos Opioides , Estudos Prospectivos , Remifentanil , SufentanilRESUMO
OBJECTIVES: To assess and compare the effectiveness and safety of flexible ureteroscopy (f-URS) with a novel flexible ureteral access sheath (f-UAS) versus mini-percutaneous nephrolithotripsy (mini-PCNL) in treating 2-3 cm renal stones. METHODS: Retrospectively analyzed consecutive cases that underwent f-URS with f-UAS (12/14 Fr) from January 29, 2022, to November 30, 2022. Consecutive cases that underwent mini-PCNL (18 Fr) from June 5, 2021, to January 26, 2022, were selected as controls. The f-UAS is a novel device with a 10 cm anterior tip that passively bends along with the f-URS to enter the renal calyx. We analyzed demographic characteristics, stone parameters, operative time, stone-free rates (SFR), hospitalization time, and complication. RESULTS: A total of 96 consecutive cases that underwent f-URS with f-UAS and 96 consecutive cases that underwent mini-PCNL were included in the study. There were no significant differences between the two groups in terms of operative time (p = 0.06), stone volume clearance (p = 0.533) and complete SFR (p = 0.266) on the first postoperative day or residual Stone after 1 month (p = 0.407). We observed a significantly shorter postoperative hospital stay (1.4 days vs. 2.1 days; p < 0.001) and a lower decrease in hemoglobin levels (0.39 g/dL vs. 0.68 g/dL; p < 0.001) in the f-UAS group. The mini-PCNL group had a significantly higher overall complication rate (13.5%) compared with the f-UAS group (5.2%; p = 0.048). CONCLUSIONS: In the treatment of 2-3 cm renal stones, f-URS with a novel f-UAS may provide a superior alternative to mini-PCNL, potentially challenging its established status.
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Cálculos Renais , Litotripsia , Nefrolitotomia Percutânea , Humanos , Cálculos Renais/cirurgia , Nefrolitotomia Percutânea/efeitos adversos , Ureteroscopia/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Non-coding RNAs (ncRNAs) are widely involved in cancer metastatic events (CMEs, e.g., cancer cell invasion, intravasation, extravasation, proliferation), which collaboratively accelerate tumor spread and cause high patient mortality. In early 2020, we developed a manually curated database named 'lncR2metasta' to provide a comprehensive repository for long ncRNA (lncRNA) regulation during CMEs. We updated this database by supplementing other two important ncRNA types, microRNAs (miRNAs) and circular RNAs (circRNAs), for their involvement during CMEs after a thorough manual curation from published studies. ncR2metasta documents 1565 lncRNA-associated, 882 miRNA-associated, and 628 circRNA-associated entries for ncRNA-CME associations during 50 CMEs across 63 human cancer subtypes. ncR2Met has a concise web interface for researchers to easily browse, search and download as well as to submit novel ncRNA-CME associations. We anticipated that it could be a valuable resource, which will significantly improve our understanding of ncRNA functions in metastasis. It is freely available at http://ncr2met.wchoda.com.
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MicroRNAs , Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/genética , Bases de Dados Factuais , RNA Circular/genéticaRESUMO
The time evolution of the total number of free electrons in the Earth's ionosphere, i.e., the Global Electron Content (GEC), during more than two solar cycles is analyzed in this work. The GEC time series has been extracted from the Global Ionospheric Maps (GIMs) of Vertical Total Electron Content (VTEC) estimated by UPC-IonSAT with TOMION-v1 software from global GPS measurements since the end of 1996. A dual-layer voxel-based tomographic model solved with a forward Kalman scalar filter, from dual-frequency carrier GPS data only, provides the so-called UQRG GIM after VTEC kriging interpolation, with a resolution of 15 min in time, 5° in longitude and 2.5° in latitude. UQRG is one of the best behaving GIMs in the International GNSS Service (IGS).In this context, the potential application of the GEC spectrum evolution as a potential space weather index is discussed and demonstrated.
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The rapid transition of agricultural systems substantially affects residential and industrial land use systems in rural areas, often generating spatiotemporal trade-offs between residential and industrial functions and producing considerable ecological impacts, which has thus far not been well understood. We conduct an indicator-based assessment of transitioning agriculture systems, and then links the transitioning agricultural systems to trade-offs between residential and industrial functions from 2005 to 2020 by using a case study-the metropolitan suburbs of Beijing, China. Also, the associated ecological impacts of the trade-offs are characterized based on the calculation of the ecological quality index (EQI) and ecological contribution rate. The results show that trade-offs between residential and industrial functions in the metropolitan suburbs have gradually adapted to the different agricultural systems in transition, which can be characterized by increasing industrial function as well as declining residential function, together with the diversification of land use into a mixed pattern. Additionally, along with the transitioning process comes a U shape of the ecological quality curve, which indicates that relentless industrial sprawl into regions where the agricultural system has a low capacity for technology, as well as decay in rural areas attributed to a rural exodus and industrial decline in semi-subsistence agricultural areas, even cause ecological degradation. In general, trade-offs between residential and industrial functions (especially for the non-agricultural production function) in rural areas could partially and temporally generate unfavorable ecological impacts, but it seems to be a favorable phenomenon to promote ecological quality in the long term. Therefore, to achieve rural sustainable planning, it is necessary for land use management to observe the trade-offs between residential and industrial functions while avoiding negative impacts, such as low-density land use patterns, disordered land use functions, and eco-environmental deterioration. Such effective strategies can contribute to the feasible implementation of policies aiming to achieve the compatible development of liveable residences, highly efficient industrial production, and eco-friendly operations in rural areas.
Assuntos
Agricultura , China , Indústrias , Conservação dos Recursos Naturais , População Rural , EcologiaRESUMO
ACYL-CoA-BINDING PROTEINs (ACBPs) play crucial regulatory roles during plant response to hypoxia, but their molecular mechanisms remain poorly understood. Our study reveals that ACBP4 serves as a positive regulator of the plant hypoxia response by interacting with WRKY70, influencing its nucleocytoplasmic shuttling in Arabidopsis thaliana. Furthermore, we demonstrate the direct binding of WRKY70 to the ACBP4 promoter, resulting in its upregulation and suggesting a positive feedback loop. Additionally, we pinpointed a phosphorylation site at Ser638 of ACBP4, which enhances submergence tolerance, potentially by facilitating WRKY70's nuclear shuttling. Surprisingly, a natural variation in this phosphorylation site of ACBP4 allowed A. thaliana to adapt to humid conditions during its historical demographic expansion. We further observed that both phosphorylated ACBP4 and oleoyl-CoA can impede the interaction between ACBP4 and WRKY70, thus promoting WRKY70's nuclear translocation. Finally, we found that the overexpression of orthologous BnaC5.ACBP4 and BnaA7.WRKY70 in Brassica napus increases submergence tolerance, indicating their functional similarity across genera. In summary, our research not only sheds light on the functional significance of the ACBP4 gene in hypoxia response, but also underscores its potential utility in breeding flooding-tolerant oilseed rape varieties.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Ligação a DNA , Fosforilação , Regiões Promotoras Genéticas/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genéticaRESUMO
Zika virus (ZIKV) is a mosquito-borne RNA virus that belongs to the Flaviviridae family. While flavivirus replication is known to occur in the cytoplasm, a significant portion of the viral capsid protein localizes to the nucleus during infection. However, the role of the nuclear capsid is less clear. Herein, we demonstrated SERTA domain containing 3 (SERTAD3) as an antiviral interferon stimulatory gene product had an antiviral ability to ZIKV but not JEV. Mechanistically, we found that SERTAD3 interacted with the capsid protein of ZIKV in the nucleolus and reduced capsid protein abundance through proteasomal degradation. Furthermore, an eight amino acid peptide of SERTAD3 was identified as the minimum motif that binds with ZIKV capsid protein. Remarkably, the eight amino acids synthetic peptide from SERTAD3 significantly prevented ZIKV infection in culture and pregnant mouse models. Taken together, these findings not only reveal the function of SERTAD3 in promoting proteasomal degradation of a specific viral protein but also provide a promising host-targeted therapeutic strategy against ZIKV infection.