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Mulberry crinkle leaf virus (MCLV), identified in mulberry plants (Morus alba L.), is a member of the genus Mulcrilevirus in the family Geminiviridae. The functions of the V2 protein encoded by MCLV remain unclear. Here, Agrobacterium-mediated infectious clones of a wild-type MCLV vII (MCLVWT) and two V2 mutant MCLV vIIs, including MCLVmV2 (with a mutation of the start codon of the V2 ORF) and MCLVdV2 (5'-end partial deletion of the V2 ORF sequence), were constructed to investigate the roles of V2 both in planta and at the cellular level. Although all three constructs (pCA-1.1MCLVWT, pCA-MCLVmV2, and pCA-MCLVdV2) were able to infect both natural host mulberry plants and experimental tomato plants systematically, the replication of the MCLVmV2 and MCLVdV2 genomes in these hosts was significantly reduced compared to that of MCLVWT. Similarly, the accumulation of MCLVmV2 and MCLVdV2 in protoplasts of Nicotiana benthamiana plants was significantly lower than that of MCLVWT either 24 h or 48 h post-transfection. A complementation experiment further confirmed that the decreased accumulation of MCLV in the protoplasts was due to the absence of V2 expression. These results revealed that MCLV-encoded V2 greatly enhances the level of MCLV DNA accumulation and is designated the replication enhancer protein of MCLV.
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Morus , Nicotiana , Proteínas Virais , Replicação Viral , Morus/genética , Morus/virologia , Replicação Viral/genética , Nicotiana/virologia , Nicotiana/genética , Proteínas Virais/genética , Proteínas Virais/metabolismo , Genoma Viral , DNA Viral/genética , DNA Viral/metabolismo , Doenças das Plantas/virologia , Doenças das Plantas/genética , Replicação do DNA/genética , Carmovirus/genética , Solanum lycopersicum/virologia , Solanum lycopersicum/genéticaRESUMO
The electrochemical activation of inert CO2 molecules through CâC coupling reactions under ambient conditions remains a significant challenge but holds great promise for sustainable development and the reduction of CO2 emission. Lewis pairs can capture and react with CO2, offering a novel strategy for the electrosynthesis of high-value-added C2 products. Herein, an electron-beam irradiation strategy is presented for rapidly synthesizing a metal-organic framework (MOF) with well-defined Lewis pairs (i.e., Cu- Npyridinic). The synthesized MOFs exhibit a total C2 product faradic efficiency of 70.0% at -0.88 V versus RHE. In situ attenuated total reflection Fourier transform infrared and Raman spectra reveal that the electron-deficient Lewis acidic Cu sites and electron-rich Lewis basic pyridinic N sites in the ligand facilitate the targeted chemisorption, activation, and conversion of CO2 molecules. DFT calculations further elucidate the electronic interactions of key intermediates in the CO2 reduction reaction. The work not only advances Lewis pair-site MOFs as a new platform for CO2 electrochemical conversion, but also provides pioneering insights into the underlying mechanisms of electron-beam irradiated synthesis of advanced nanomaterials.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Sorafenibe/uso terapêuticoRESUMO
BACKGROUND: Despite the well-established regulatory role of vitamin D in maintaining bone health, little is known about the shared genetics and causality of the association between serum 25-hydroxyvitamin D (25OHD) and bone mineral density (BMD). METHODS: Leveraging individual-level data from the UK Biobank (UKB) cohort and summary-level data from the genome-wide association studies (GWASs) conducted on European individuals for serum 25OHD (N = 417,580) and estimated heel BMD (eBMD, N = 426,824), we systematically elucidated the shared genetic architecture underlying serum 25OHD and eBMD through a comprehensive genome-wide cross-trait design. RESULTS: Despite a lack of global genetic correlation (rg = -0.001, P = 0.95), a significant local signal was discovered at 5p11-5q11.9. Two-sample Mendelian randomization (MR) indicated no causal association in the overall population (ß = 0.003, 95% CI = -0.04â¼0.03, P = 0.93), while positive causal effects were observed in males (ß = 0.005, 95% CI = 0.00â¼0.01, P = 0.03) and the elderly (ß = 0.009, 95% CI = 0.00â¼0.02, P = 0.01) according to one-sample MR. A total of 49 pleiotropic SNPs, with 4 novel SNPs (rs1077151, rs79873740, rs12150353, and rs4760401), were identified, and a total of 95 gene-tissue pairs exhibited overlap, predominantly enriched in the nervous, digestive, exo-/endocrine and cardiovascular systems. Protein-protein interaction analysis identified RPS9 and RPL7A as hub genes. CONCLUSIONS: This study illuminates the potential health benefits of enhancing serum 25OHD levels to mitigate the risk of osteoporosis among males and the elderly. It also unveils a shared genetic basis between serum 25OHD and eBMD, offering valuable insights into the intricate biological pathways.
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BACKGROUND: Balance and mobility deficits are major concerns in stroke rehabilitation. Virtual reality (VR) training and Swiss-ball training are commonly used approaches to improve balance and mobility. However, no study has compared the efficacy of VR training, Swiss-ball training, and their combination in improving balance and mobility function or investigated cortical activation and connectivity in individuals with stroke. METHODS: A prospective, single-blinded, parallel-armed, multi-center randomized controlled trial with factorial design will be conducted. Seventy-six participants aged 30-80 years with stroke will be recruited. Participants will be allocated to one of the four groups: (A) the VR training + Swiss-ball training + conventional physical therapy group; (B) the Swiss-ball training + conventional physical therapy group; (C) the VR training + conventional physical therapy group; or (D) the conventional physical therapy group. All participants will receive 50 min of training per day, 5 times per week, for a total of 4 weeks. The primary outcomes will be balance and mobility measures. Secondary outcomes will include the 10-min walk test, dynamic gait index, and cortical activation. Outcomes will be measured on three occasions: at baseline, after the training, and at the 4-week follow-up. DISCUSSION: This trial will provide evidence to determine whether there are differences in clinical outcomes and cortical activation following two different types of exercise programs and their combination, and to elucidate the recovery mechanisms of balance and mobility function in individuals with stroke. TRIAL REGISTRATION: Chinese Clinical Trial Registry reference: www.chictr.org.cn (No. ChiCTR2400082135). Registered on May 24, 2024.
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Estudos Multicêntricos como Assunto , Equilíbrio Postural , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Reabilitação do Acidente Vascular Cerebral/métodos , Pessoa de Meia-Idade , Idoso , Método Simples-Cego , Estudos Prospectivos , Masculino , Adulto , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Feminino , Idoso de 80 Anos ou mais , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Terapia de Exposição à Realidade Virtual/métodos , Recuperação de Função Fisiológica , Realidade Virtual , Doença Crônica , Terapia por Exercício/métodos , Fatores de Tempo , Modalidades de FisioterapiaRESUMO
Arginine plays a key role in regulating the immune function of fish. To evaluate the effect of arginine on the immune response of largemouth bass (Micropterus salmoides), the effects of arginine on cell viability, NADPH oxidase activity, respiratory burst activity, and NO production of leukocytes were analyzed both in vitro and in vivo. In this study, we found that arginine could promote the respiratory burst activity of leucocytes both in vivo and in vitro. By incubating leukocytes with the combination of LPS and arginine, we found that arginine supplementation inhibited the expression of inflammatory genes (tumor necrosis factor-alpha, tnfα; interleukin(il) 8 and il10) and apoptotic genes (caspase 3, caspase 8, and caspase 9) induced by LPS, as well as promoted the arginine metabolism. Arginine supplementation significantly induced (cd4-like) cd4 gene expression after LPS challenge. Further studies showed that LPS could significantly increase nucleotide-binding oligomerization domain containing 1 (nod1) gene expression, but decreased the nod2 gene. The arginine supplementation increased nuclear factor kappa-B (NF-κB) protein level. In conclusion, arginine can alleviate LPS-induced inflammatory response and apoptosis as well as induce cd4 gene expression against LPS challenge via adjusting the expression of NODs signaling.
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Photodetectors based on advanced materials with a broad spectral photoresponse, high sensitivity, huge integration ability, room-temperature operation, and stable environmental stability are highly desired for diversified applications of imaging, sensing, and communication. Herein, a high-performance ultra-broadband photodetector based on an ultrathin two-dimensional (2D) Fe3O4 nanoflake heterostructure with high sensitivity was designed. The photodetector response light was from visible 405 nm to long-wave infrared (LWIR) 10.6 µm in ambient air. The competitive performances, including a high photoresponsivity (R) of 182.8 A W-1, fast speed with the rise time τr = 8.8 µs, and decay time τd = 4.1 µs, were demonstrated in the visible range. Notably, the device exhibits an excellent uncooled LWIR detection ability, with a high R of 1.4 A W-1 realized at a 1.5 V bias. In the full spectral range, the noise equivalent power is lower than 0.79 pW Hz-1/2, and specific detectivity (D*) is higher than 4.9 × 108 cm Hz1/2 W-1 in ambient air. This work provides alternative ultrathin 2D materials for future infrared optoelectronic devices.
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Vaccination plays a crucial role in preventing and controlling SARS-CoV-2 infections as well as their associated adverse outcomes. But there is a notable lack of research on the effectiveness of COVID-19 vaccination in children, particularly those young preterm-born children, who are more vulnerable to severe outcomes from SARS-CoV-2 infection. We aimed to determine the effect of vaccination with inactivated vaccines BBIBP-CorV and CoronaVac on symptomatic COVID-19 infection and related symptoms in preterm-born children aged 3-7 years after relaxation of the COVID-19 prevention and control measures in December 2022 in China. We performed a retrospective cohort study involving 242 preterm-born children aged 3-7 years and the data were collected in March 2023. Logistic regression models and modified Poisson regression models combined with entropy balancing were used to explore the associations of vaccination against SARS-CoV-2 with symptomatic COVID-19, specific symptoms, and persistent symptoms one month after recovery from COVID-19. Of the 242 recruited preterm-born children, 156 (64.5%) were vaccinated with inactivated vaccines BBIBP-CorV and CoronaVac. After entropy balancing, the covariates were balanced between the vaccinated and the unvaccinated groups, with standardized mean difference < 0.001. Vaccination with the said SARS-CoV-2 vaccines lowered the risk of developing symptomatic COVID-19 in preterm-born children (risk ratio [RR] = 0.783; 95% confidence interval [CI]: (0.711, 0.861). Likewise, COVID-19 vaccination was associated with a decline in the risk of pneumonia (odds ratio [OR] = 0.318; 95% CI 0.110, 0.913), fever (RR = 0.710; 95% CI 0.635, 0.794), high fever (RR = 0.542; 95% CI 0.297, 0.988), sore throat (OR = 0.304; 95% CI 0.139, 0.664), and persistent symptoms (RR = 0.425; 95% CI 0.182, 0.993). Immunization with inactivated vaccines BBIBP-CorV and CoronaVac provides protection against symptomatic COVID-19 for preterm-born children 3-7 years.
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Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Vacinação , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , China/epidemiologia , Feminino , Masculino , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Estudos Retrospectivos , Pré-Escolar , SARS-CoV-2/imunologia , Criança , Vacinas de Produtos Inativados/administração & dosagem , Recém-Nascido Prematuro , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Nascimento Prematuro/prevenção & controleRESUMO
Background: Lymphovascular invasion (LVI) and perineural invasion (PNI) are important histopathological variables that are directly related to the survival and recurrence of patients with colorectal cancer (CRC). Preoperative prediction of LVI and PNI status in CRC is helpful in selecting patients requiring appropriate adjuvant therapy and evaluating prognosis. This study aimed to investigate the value of combining single-source dual-energy computed tomography (ssDECT)-derived parameters with extracellular volume (ECV) fraction for preoperative evaluation of LVI and PNI in CRC. Methods: This retrospective study included patients with CRC who underwent contrast-enhanced ssDECT. All diagnoses were confirmed through histopathology, and the patients were classified into positive and negative groups based on the presence of LVI/PNI. Clinical data were collected. In the arterial (AP), venous (VP) and delayed phases (DP), the ssDECT-derived parameters were measured by two radiologists. The measurement consistency was evaluated using intraclass correlation coefficients. Differences between the two groups were analyzed using the t-test, Mann-Whitney U test, or Chi-square test. Binary logistic regression was employed to construct models incorporating multiple parameters. The diagnostic performance of various parameters or models was assessed by analyzing receiver operating characteristic curves. Results: In total, 118 patients with CRC were included in the study. Serum carcinoembryonic antigen levels, T and N stages, and histological grades differed between the two groups (all P<0.05). The ssDECT-derived parameters in the VP and DP of LVI/PNI-positive group were higher than those of -negative group (all P<0.05). The ECV fraction in the DP of LVI/PNI-positive group was higher than that of -negative group (P=0.001). Discriminating capability analysis demonstrated that the diagnostic efficacies of the DP parameters were superior to those of the VP parameters, and the normalized iodine concentration in the DP exhibited the best performance [area under the curve (AUC): 0.750; 95% confidence interval (CI): 0.648-0.852]. The combination of ECV DP with clinical and ssDECT-derived parameters demonstrated the highest discriminative capability (AUC: 0.857; 95% CI: 0.786-0.928). Conclusions: ssDECT-derived parameters and ECV fraction may serve as non-invasive tools for predicting the LVI/PNI status in CRC.
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Background: Pulmonary nodules with Lung Imaging Reporting and Data System (Lung-RADS) 4X are of greater clinical significance, and accurate differentiation of pathological types and visceral pleural invasion (VPI) of Lung-RADS 4X peripheral pulmonary nodules before treatment can aid in stratification. This study set out to investigate whether the tumour-pleura relationship on computed tomography (CT) can provide effective risk stratification for peripheral pulmonary nodules with Lung-RADS 4X. Methods: This was a single institution, retrospective study of 482 consecutive patients with Lung-RADS score 4X, who were pathologically diagnosed with tuberculous granuloma and adenocarcinoma from January 2019 to December 2023. We assessed clinical factors (baseline characteristics and tumour markers) and CT findings. Univariate and multivariate logistic regression analyses were used to determine the classification of pulmonary nodules and predictors of VPI. Results: Multivariate analysis revealed that gender [odds ratio (OR) =0.392; P<0.001], carcinoembryonic antigen (CEA) level (OR =8.331; P<0.001), type of nodules (OR =13.551 and 7.478; P<0.001 and P=0.016) and maximum base width of soft tissue component on the pleura side (OR =0.857; P=0.005) were significant independent factors for distinguishing tuberculous granuloma from adenocarcinoma. And the type of linear connection between lesion and pleura (OR =3.936; P<0.001), and the maximum base width of soft tissue components on the pleura side (OR =1.359; P=0.001) were correlated independently with VPI. The area under the curve (AUC) for predicting pulmonary nodules classification was 82.60% [95% confidence interval (CI): 78.85-86.35%), and the AUC for predicting VPI was 76.10% (95% CI: 69.83-82.38%). Conclusions: The tumour-pleura relationship will be helpful in further risk stratification for peripheral pulmonary nodules with a score of Lung-RADS 4X.
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BACKGROUND: In China banxia xiexin decoction (BXD) has been used in treating gastric cancer (GC) for thousands of years and BXD has a good role in reversing GC histopathology, but its chemical composition and action mechanism are still unknown. AIM: To investigate the mechanism of action of BXD against GC based on transcriptomics, network pharmacology, in vivo and in vitro experiments. METHODS: The transplanted tumor model was prepared, and the nude mouse were pathologically examined after administration, and hematoxylin-eosin staining was performed. The active ingredients of BXD were quality controlled and identified using ultra-performance liquid chromatography tandem quadrupole electrostatic field orbitrap mass spectrometry (UPLC-Q-Orbitrap MS/MS), and traditional Chinese medicines systems pharmacology platform, drug bank and the Swiss target prediction platform to predict the relevant targets, the differentially expressed genes (DEGs) of GC were screened by RNA-seq sequencing, and the overlapping targets were analyzed to obtain the key targets and pathways. Cell Counting Kit-8, apoptosis assay, cell migration and Realtime fluorescence quantitative polymerase chain reaction were used for in vitro experiments. RESULTS: All dosing groups inhibited the growth of transplanted tumors in laboratory-bred strain nude, with the capecitabine group and the BXD medium-dose group being the best. A total of 29 compounds and 859 potential targets in BXD were identified by UPLC-Q-Orbitrap MS/MS and network pharmacology, RNA-seq sequencing found 4767 GC DEGs, which were combined with network pharmacology and analyzed 246 potential therapeutic targets were obtained and pathway results showed that BXD may against GC through the Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKt) signaling pathway. In vitro cellular experiments confirmed that BXD-containing serum and LY294002 could inhibit the proliferation of GC cells, promote apoptosis, and inhibit the migration of GC cells by decreasing the expression of EGFR, PIK3CA, IL6, BCL2 and AKT1 in the PI3K-Akt pathway in MGC-803 expression. CONCLUSION: BXD has the effect of inhibiting tumor growth rate and delaying the development of GC. Its mechanism of action may be related to the regulation of PI3K-Akt signaling pathway.
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Objective: This study aimed to investigate the roles of neurotrophic factors (NTFs), monoamine neurotransmitters, and inflammatory processes in the pathophysiology of the comorbidity of epilepsy and depression. Methods: A retrospective analysis was conducted with 57 epilepsy patients (PWE), 50 patients with epilepsy and comorbid depression (PWECD), and 47 healthy controls (HC) admitted between June 2020 and June 2024. Serum levels of brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), 5-hydroxytryptamine (5-HT), norepinephrine (NE), dopamine (DA), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were measured using enzyme-linked immunosorbent assay (ELISA). Additionally, BDNF and GDNF levels in cerebrospinal fluid (CSF) samples were analyzed from selected patients in the PWE and PWECD groups. Results: Serum BDNF levels were significantly lower in both PWE and PWECD groups compared to HC, while no differences between the former two groups. GDNF levels were lower in PWECD compared to HC, but not between PWE and HC. Serum 5-HT was significantly reduced in PWECD compared to both HC and PWE groups. No significant differences were observed in serum DA, NE, and IL-6 levels across the groups. Serum IL-1ß levels were elevated in the PWECD group compared to the HC group. The Self-Rating Depression Scale (SDS) score negatively correlated with serum 5-HT and GDNF levels. In terms of predictive ability, serum BDNF demonstrated higher accuracy for the diagnosis of epilepsy [area under the curve, AUC = 0.701, 95% confidence intervals (95% CI) 0.601 ~ 0.801], while serum 5-HT was the best marker for predicting the development of depression in epilepsy patients (AUC = 0.727, 95% CI 0.632 ~ 0.821). No significant correlation was found between serum and CSF BDNF levels within the same subject (r = 0.155; p = 0.221; Spearman correlation), and CSF GDNF levels were too low to be clinically informative. Conclusion: The findings suggest the involvement of NTFs, monoamine neurotransmitters, and inflammatory processes in the pathogenesis of epilepsy and depression. Decreased serum BDNF levels correlate with epilepsy but not necessarily with comorbid depression, while serum GDNF and 5-HT show potential clinical value in diagnosing this comorbidity. However, the deficient levels of NTFs in CSF suggest a need for more sensitive detection methods.
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Elevated ribosome biogenesis correlates with the rapid growth and progression of cancer. Targeted blockade of ribosome biogenesis induces nucleolar stress, which preferentially leads to the elimination of malignant cells. In this study, it is reported that the nucleolar protein BRIX1 is a critical regulator for the homeostasis between ribosome biogenesis and p53 activation. BRIX1 facilitated the processing of pre-rRNA by supporting the formation of the PeBoW complex. In addition, BRIX1 prevented p53 activation in response to nucleolar stress by impairing the interactions between MDM2 and the ribosomal proteins, RPL5, and RPL11, thereby triggering the resistance of cancer cells to chemotherapy. Conversely, depletion of BRIX1 induced nucleolar stress, which in turn activated p53 through RPL5 and RPL11, consequently inhibiting the growth of tumors. Moreover, engineered exosomes are developed, which are surface-decorated with iRGD, a tumor-homing peptide, and loaded with siRNAs specific to BRIX1, for the treatment of cancer. iRGD-Exo-siBRIX1 significantly suppressed the growth of colorectal cancer and enhanced the efficacy of 5-FU chemotherapy in vivo. Overall, the study uncovers that BRIX1 functions as an oncoprotein to promote rRNA synthesis and dampen p53 activity, and also implies that targeted inhibition of BRIX1 via engineered exosomes can be a potent approach for cancer therapy.
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The task-space distributed adaptive neural network (NN) fixed-time tracking problem is studied for networked heterogeneous robotic systems (NHRSs). In order to address this complex problem, we propose a NN-based fixed-time hierarchical control approach that transforms the problem into two sub-problems: a distributed fixed-time estimation problem and a local fixed-time tracking problem, respectively. Specifically, distributed estimators are constructed so that each follower can acquire the dynamic leader's state in a fixed time. Then, the neural networks (NNs) are employed to approximate the compounded uncertainty consisting of the unknown dynamics of robotic systems and the boundary of the compounded disturbance. More importantly, to guarantee that the tracking errors can converge into a small neighborhood of equilibrium in a fixed time independent of the initial state, the adaptive neural fixed-time local tracking controller is proposed. Another merit of the proposed controller is that the approximation errors are addressed in a novel way, eliminating the need for prior precise knowledge of uncertainties and improving the robustness and convergence speed of unknown robotic systems. Finally, the experimental results demonstrate the effectiveness and advantages of the proposed control method.
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INTRODUCTION: The safety and efficacy of liraglutide as a weight loss intervention in individuals who remain obese within 1 year post-metabolic surgery remain unclear. This study aimed to evaluate the effects and safety of liraglutide (1.8 mg) in patients with persistent obesity at 6 months postoperatively. METHODS: This retrospective cohort study included 61 patients who remained obese (body mass index [BMI] ≥ 28.0 kg/m2) at 6 months postoperatively. Among these patients, 27 were treated with 1.8 mg of liraglutide for 12 weeks, whereas 34 served as controls. The primary endpoint was the change in total weight loss (%TWL) after 24 weeks. Changes in weight, BMI, complications, and adverse events were also assessed. RESULTS: The liraglutide group showed a greater reduction in %TWL than the control group (11.6% ± 1.1% vs. 4.9% ± 1.0%), with an estimated treatment difference of 6.6% (95% confidence interval [CI], 3.7-9.6%, P < 0.01). The adjusted mean differences in the reduction of weight and BMI between the liraglutide and control groups were - 6.2 kg (95% CI - 8.9 to - 3.4, P < 0.01) and - 3.0 kg/m2 (95% CI - 4.2 to - 1.7, P < 0.01), respectively. The liraglutide group exhibited increased rates of remission in non-alcoholic fatty liver disease and hypertension. No serious adverse reactions were observed. CONCLUSIONS: For patients who remained obese at 6 months postoperatively, 12-week liraglutide treatment resulted in increased weight loss, improved metabolic control, and high rate of remission for obesity-related metabolic diseases after 24 weeks. Earlier and more timely adjuvant weight loss medication intervention based on BMI within 1 year postoperatively may enhance weight loss after metabolic surgery. Graphical abstract available for this article.
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Cytoskeleton remodeling which generates force and orchestrates signaling and trafficking to govern cell migration remains poorly understood, partly due to a lack of an investigation tool with high system flexibility, spatiotemporal resolution, and computational sensitivity. Herein, we developed a multimodal superresolution imaging system-based architecture-driven quantitative (ADQ) framework in spatiotemporal-angular hyperspace to enable both identification of the optimal imaging mode with well-balanced fidelity and phototoxicity and accurate postcharacterization of microtubule remodeling. In the ADQ framework, a pixel/voxel-wise metric reflecting heterogeneous intertubule alignment was proposed with improved sensitivity over previous efforts and further incorporated with temporal features to map dynamic microtubule rearrangements. The ADQ framework was verified by assessing microtubule remodeling in drug-induced (de)polymerization, lysosome transport, and migration. Different remodeling patterns from two migration modes were successfully revealed by the ADQ framework, with a front-rear polarization for individual directed migration and a contact site-centered polarization for cell-cell interaction-induced migration in an immune response model. Meanwhile, these migration modes were found to have consistent orientation changes, which exhibited the potential of predicting migration trajectory.
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Movimento Celular , Citoesqueleto , Microtúbulos , Microtúbulos/metabolismo , Humanos , Citoesqueleto/metabolismo , Lisossomos/metabolismoRESUMO
In view of the current problems of slow crystallization rate, varying grain sizes, complex process conditions, and low safety in the preparation of CL-20/TNT cocrystal explosives in the laboratory, an opposite spray crystallization method is provided to quickly prepare ultrafine explosive cocrystal particles. CL-20/TNT cocrystal explosive was prepared using this method, and the obtained cocrystal samples were characterized by electron microscopy morphology, differential thermal analysis, infrared spectroscopy, and X-ray diffraction analysis. The effects of spray temperature, feed ratio, and preparation method on the formation of explosive cocrystal were studied, and the process conditions of the pneumatic atomization spray crystallization method were optimized. The crystal plane binding energy and molecular interaction forces between CL-20 and TNT were obtained through molecular dynamic simulation, and the optimal binding crystal plane and cocrystal mechanism were analyzed. The theoretical calculation temperature of the binding energy was preliminarily explored in relation to the preparation process temperature of cocrystal explosives. The mechanical sensitivity of ultrafine CL-20/TNT cocrystal samples was tested. The results showed that choosing acetone as the cosolvent, a spraying temperature of 30 °C, and a feeding ratio of 1:1 was beneficial for the formation and growth of cocrystal. The prepared CL-20/TNT cocrystal has a particle size of approximately 10 µm. The grain size is small, and the crystallization rate is fast. The impact and friction sensitivity of ultrafine CL-20/TNT cocrystal samples were significantly reduced. The experimental process conditions are simple and easy to control, and the safety of the preparation process is high, providing certain technical support for the preparation of high-quality cocrystal explosives.
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Cristalização , Substâncias Explosivas , Simulação de Dinâmica Molecular , Trinitrotolueno , Cristalização/métodos , Substâncias Explosivas/química , Trinitrotolueno/química , Difração de Raios X , TemperaturaRESUMO
Path planning is a key problem in the autonomous navigation of mobile robots and a research hotspot in the field of robotics. Harris Hawk Optimization (HHO) faces challenges such as low solution accuracy and a slow convergence speed, and it easy falls into local optimization in path planning applications. For this reason, this paper proposes a Multi-strategy Improved Harris Hawk Optimization (MIHHO) algorithm. First, the double adaptive weight strategy is used to enhance the search capability of the algorithm to significantly improve the convergence accuracy and speed of path planning; second, the Dimension Learning-based Hunting (DLH) search strategy is introduced to effectively balance exploration and exploitation while maintaining the diversity of the population; and then, Position update strategy based on Dung Beetle Optimizer algorithm is proposed to reduce the algorithm's possibility of falling into local optimal solutions during path planning. The experimental results of the comparison of the test functions show that the MIHHO algorithm is ranked first in terms of performance, with significant improvements in optimization seeking ability, convergence speed, and stability. Finally, MIHHO is applied to robot path planning, and the test results show that in four environments with different complexities and scales, the average path lengths of MIHHO are improved by 1.99%, 14.45%, 4.52%, and 9.19% compared to HHO, respectively. These results indicate that MIHHO has significant performance advantages in path planning tasks and helps to improve the path planning efficiency and accuracy of mobile robots.
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Background: The important role of nucleobindin 2 (NUCB2) in various cancers has been recently recognized. However, its biological functions and regulatory mechanisms in hepatocellular carcinoma (HCC) remain unclear. Methods: The expression level of NUCB2 in HCC was assessed using public databases, immunohistochemistry, and Western blotting. The effects of NUCB2 on cell proliferation and metastasis were investigated using colony formation, EdU, Transwell assays, and an in vivo mouse xenograft model. Regulation of E2F4 by NUCB2 was identified by protein half-life and in vivo ubiquitylation assays. The relationship between E2F4 and prostaglandin reductase 1 (PTGR1) was investigated by qRT-PCR, RT-PCR, and chromatin immunoprecipitation assays. Results: This study found that NUCB2 expression was significantly higher in HCC tissues than in normal liver tissues, and patients with high expression displayed shorter survival rates. Inhibition of NUCB2 reduced the proliferation and metastatic potential of HCC cells in vitro and in vivo. NUCB2 depletion reduced PTGR1 expression, which reduced cell proliferation and migration. Our findings suggested that NUCB2 suppressed E2F4 degradation by interacting with E2F4. Additionally, increased E2F4 levels facilitated PTGR1 transcription by directly binding to the PTGR1 promoter. Conclusion: This study demonstrated the oncogenic properties of NUCB2 in HCC and suggested that NUCB2 facilitates hepatocellular carcinoma progression by activating the E2F4/PTGR1 axis.