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1.
Chem Sci ; 15(22): 8443-8450, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38846407

RESUMO

Isomerization reactions of unsaturated molecules offer an efficient strategy in atom-economical synthesis. Although isomerization reactions of unsaturated organic and organometallic compounds, such as alkenes, alkynes, and metal carbynes, have been achieved, those of metal vinylidene units that contain cumulated double bonds have never been reported. Herein, we inaugurally discovered isomerization reactions of metal vinylidene units via protonation and deprotonation reactions of metal carbenes. Experimental and theoretical investigations indicate that the electrical characteristics of substituents on the rings play a crucial role in controlling the formation of metal vinylidene units. The isomerization reactions of metal vinylidene units were driven by thermodynamic forces. Moreover, one of the angles at metal vinylidenes was found as 126.9°, representing the smallest angle in metal vinylidenes and the first cyclic 4d transition metal (Ru) vinylidene complex was successfully isolated. These investigations unveil novel structures and reactivity for metal vinylidenes, offering a fresh perspective on the isomerization reactions of unsaturated molecules containing cumulative unsaturated bonds.

2.
BMC Med ; 22(1): 244, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38867192

RESUMO

BACKGROUND: Intracerebral hemorrhage (ICH) is a common stroke type with high morbidity and mortality. There are mainly three surgical methods for treating ICH. Unfortunately, thus far, no specific surgical method has been proven to be the most effective. We carried out this study to investigate whether minimally invasive surgeries with endoscopic surgery or stereotactic aspiration (frameless navigated aspiration) will improve functional outcomes in patients with supratentorial ICH compared with small-bone flap craniotomy. METHODS: In this parallel-group multicenter randomized controlled trial conducted at 16 centers, patients with supratentorial hypertensive ICH were randomized to receive endoscopic surgery, stereotactic aspiration, or craniotomy at a 1:1:1 ratio from July 2016 to June 2022. The follow-up duration was 6 months. Patients were randomized to receive endoscopic evacuation, stereotactic aspiration, or small-bone flap craniotomy. The primary outcome was favorable functional outcome, defined as the proportion of patients who achieved a modified Rankin scale (mRS) score of 0-2 at the 6-month follow-up. RESULTS: A total of 733 patients were randomly allocated to three groups: 243 to the endoscopy group, 247 to the aspiration group, and 243 to the craniotomy group. Finally, 721 patients (239 in the endoscopy group, 246 in the aspiration group, and 236 in the craniotomy group) received treatment and were included in the intention-to-treat analysis. Primary efficacy analysis revealed that 73 of 219 (33.3%) in the endoscopy group, 72 of 220 (32.7%) in the aspiration group, and 47 of 212 (22.2%) in the craniotomy group achieved favorable functional outcome at the 6-month follow-up (P = .017). We got similar results in subgroup analysis of deep hemorrhages, while in lobar hemorrhages the prognostic outcome was similar among three groups. Old age, deep hematoma location, large hematoma volume, low preoperative GCS score, craniotomy, and intracranial infection were associated with greater odds of unfavorable outcomes. The mean hospitalization expenses were ¥92,420 in the endoscopy group, ¥77,351 in the aspiration group, and ¥100,947 in the craniotomy group (P = .000). CONCLUSIONS: Compared with small bone flap craniotomy, endoscopic surgery and stereotactic aspiration improved the long-term outcome of hypertensive ICH, especially deep hemorrhages. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02811614.


Assuntos
Craniotomia , Hemorragia Intracraniana Hipertensiva , Procedimentos Cirúrgicos Minimamente Invasivos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Hemorragia Intracraniana Hipertensiva/cirurgia , Idoso , Craniotomia/métodos , Resultado do Tratamento , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Endoscopia/métodos , Adulto
3.
Surg Case Rep ; 10(1): 157, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904880

RESUMO

BACKGROUND: Meckel's diverticulum (MD) is the most common congenital abnormality of the gastrointestinal tract. However, MD is rare in clinical practice, and perforation of a MD by a foreign body is even rarer. Preoperative diagnosis is difficult because there is often insufficient information; therefore it is usually diagnosed intraoperatively. Although rare, it should be considered as a differential diagnosis in patients who have ingested foreign bodies. CASE PRESENTATION: The following is the case of a 52-year-old female patient who was admitted because of generalized abdominal pain for 5 days, related to nausea and vomiting. She also stopped passing gas. Inflammatory indicators were elevated, and computed tomography (CT) revealed gas-liquid levels in the small intestine and high-density objects in the ileum. Based on the patient's condition, laparotomy was performed instead because the laparoscopic procedure was difficult to perform. Intraoperatively, a foreign body perforated the diverticulum of the terminal ileum, resulting in the development of an abdominal abscess. Finally, we performed resection of the ileal diverticula and partial resection of the ileum. After the surgery, it was confirmed that the foreign bodies were two dentures accidentally eaten by the patient. CONCLUSION: A thorough understanding of the clinical presentation, imaging features, and treatment of MD and its complications will assist clinicians in making prompt and accurate diagnoses and providing symptomatic treatment.

4.
J Reprod Dev ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38910127

RESUMO

Understanding how stress hormones induce apoptosis in oviductal epithelial cells (OECs) and mural granulosa cells (MGCs) can reveal the mechanisms by which female stress impairs embryonic development and oocyte competence. A recent study showed that tissue plasminogen activator (tPA) ameliorates corticosterone-induced apoptosis in MGCs and OECs by acting on its receptors low-density lipoprotein receptor-related protein 1 (LRP1) and Annexin A2 (ANXA2), respectively. However, whether tPA is involved in corticotropin-releasing hormone (CRH)-induced apoptosis and whether it uses the same or different receptors to inhibit apoptosis induced by different hormones in the same cell type remains unknown. This study showed that CRH triggered apoptosis in both OECs and MGCs and significantly downregulated tPA expression. Moreover, tPA inhibits CRH-induced apoptosis by acting on ANXA2 in both OECs and MGCs. While ANXA2 inhibits apoptosis via phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling, LRP1 reduces apoptosis via mitogen-activated protein kinase (MAPK) signaling. Thus, tPA used the same receptor to inhibit CRH-induced apoptosis in both OECs and MGCs, however used different receptors to inhibit corticosterone-induced apoptosis in MGCs and OECs. These data helps understand the mechanism by which female stress impairs embryo/oocyte competence and proapoptotic factors trigger apoptosis in different cell types.

5.
Sci Total Environ ; : 174048, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38906282

RESUMO

RATIONALE: The association between ambient coarse particulate matter (PM2.5-10) and mortality in multi-drug resistant tuberculosis (MDR-TB) patients has not yet been studied. The modifying effects of temperature and humidity on this association are completely unknown. OBJECTIVES: To evaluate the effects of long-term PM2.5-10 exposures, and their modifications by temperature and humidity on mortality among MDR-TB patients. METHODS: A Chinese cohort of 3469 MDR-TB patients was followed up from diagnosis until death, loss to follow-up, or the study's end, averaging 2567 days per patient. PM2.5-10 concentrations were derived from the difference between PM10 and PM2.5. Cox proportional hazard models estimated hazard ratios (HRs) per 3.74 µg/m3 (interquartile range, IQR) exposure to PM2.5-10 and all-cause mortality for the full cohort and individuals at distinct long-term and short-term temperature and humidity levels, adjusting for other air pollutants and potential covariates. Exposure-response relationships were quantified using smoothed splines. RESULTS: Hazard ratios of 1.733 (95 % CI, 1.407, 2.135) and 1.427 (1.114, 1.827) were observed for mortality in association with PM2.5-10 exposures for the full cohort under long-term and short-term exposures to temperature and humidity. Modifying effects by temperature and humidity were heterogenous across sexes, age, treatment history, and surrounding living environment, measured by greenness and nighttime light levels. Nonlinear exposure-response curves suggested a cumulative risk of PM2.5-10-related mortality starting from a low exposure concentration around 15 µg/m3. CONCLUSION: Long-term exposure to PM2.5-10 poses significant harm among MDR-TB patients, with effects modified by temperature and humidity. Immediate surveillance of PM2.5-10 is crucial to mitigate the progression of MDR-TB severity, particularly due to co-exposures to air pollution and adverse weather conditions.

6.
Opt Express ; 32(9): 15444-15459, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38859194

RESUMO

The applications of rate-compatible low-density parity-check (RC-LDPC) codes are investigated for a 16 quadrature amplitude modulation (16QAM) signal and coherent detection system. With rate-compatible signals, we can provide the flexible net data rate between 135.5 Gb/s and 169.7 Gb/s in a passive optical network (PON) link. Based on the LDPC codes defined in the IEEE 802.3ca standard, we construct two sets of RC-LDPC codes with a fixed and variable information bit length. Since the puncturing operation may degrade the performance of LDPC codes, we apply the protograph-based extrinsic information transfer (PEXIT) technique to optimize the puncturing positions to mitigate the degradation. Additionally, we explore four low-complexity LDPC decoding algorithms (min sum, offset min sum, variable weight min sum, and relaxed min sum with 2nd min emulation) to investigate the relationship between the computational complexity and decoding performance. Simulation results indicate that the constructed codewords exhibit good performance in the waterfall region across a range of code rates. Finally, we conduct an experimental setup in a dual-polarization 25 GBaud 16QAM coherent PON to verify the effectiveness of the constructed LDPC codes with four decoding algorithms. The experimental results show maximal 4.8 dB receiver sensitivity differences, which demonstrate the feasibility of the method for constructing RC-LDPC codes in future high-speed flexible coherent PON.

7.
Int J Gen Med ; 17: 2719-2740, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38883702

RESUMO

Background: Aging is recognized as the key risk for intracerebral hemorrhage (ICH). The detailed mechanisms of aging in ICH warrant exploration. This study aimed to identify potential aging-related genes associated with ICH. Methods: ICH-specific aging-related genes were determined by the intersection of differentially expressed genes (DEGs) between perihematomal tissues and corresponding contralateral parts of four patients with ICH (GSE24265) and 349 aging-related genes obtained from the Aging Atlas database. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) analyses were performed to identify the potential biological functions and pathways in which these ICH-specific aging-related genes may be involved. Then, PPI network was established to identify the hub genes of ICH-specific aging-related genes. Meanwhile, miRNA-mRNA and transcription factor (TF)-mRNA regulatory networks were constructed to further explore the ICH-specific aging-related genes regulation. The relationship between these hub genes and immune infiltration was also further explored. Additional single-cell RNA-seq analysis (scRNA-seq, GSE167593) was used to locate the hub genes in different cell types. Besides, expression levels of the hub genes were validated using clinical samples from our institute and another GEO dataset (GSE206971). Results: This study identified 24 ICH-specific aging-related genes, including 22 up-regulated and 2 down-regulated genes. The results of GO and KEGG suggested that the ICH-specific aging-related genes mainly enriched in immunity and inflammation-related pathways, suggesting that aging may affect the ich pathogenesis by regulating inflammatory and immune-related pathways. Conclusion: Our study revealed 24 ICH-specific aging-related genes and their functions highly pertinent to ICH pathogenesis, providing new insights into the impact of aging on ICH.

8.
J Am Chem Soc ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899504

RESUMO

Targeted protein degradation technology holds great potential in biomedicine, particularly in treating tumors and other protein-related diseases. Research on intracellular protein degradation using molecular glues and PROTAC technology is leading, while research on the degradation of membrane proteins and extracellular proteins through the lysosomal pathway is still in the preclinical stage. The scarcity of useful targets is an immense limitation to technological advancement, making it essential to explore novel, potentially effective approaches for targeted lysosomal degradation. Here, we employed the glucose transporter Glut1 as an innovative lysosome-targeting receptor and devised the Glut1-Facilitated Lysosomal Degradation (GFLD) strategy. We synthesized potential Glut1 ligands via reversible addition-fragmentation chain transfer (RAFT) polymerization and acquired antibody-glycooligomer conjugates through bioorthogonal reactions as lysosome-targeting protein degradation molecules, utilized in the management of PD-L1 high-expressing triple-negative breast cancer. The glucose transporter Glut1 as a lysosome-targeting receptor exhibits potential for the advancement of a broader array of medications in the future.

9.
Magn Reson Med ; 92(3): 956-966, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38770624

RESUMO

PURPOSE: To demonstrate the feasibility of zigzag sampling for 3D rapid hyperpolarized 129Xe ventilation MRI in human. METHODS: Zigzag sampling in one direction was combined with gradient-recalled echo sequence (GRE-zigzag-Y) to acquire hyperpolarized 129Xe ventilation images. Image quality was compared with a balanced SSFP (bSSFP) sequence with the same spatial resolution for 12 healthy volunteers (HVs). For another 8 HVs and 9 discharged coronavirus disease 2019 subjects, isotropic resolution 129Xe ventilation images were acquired using zigzag sampling in two directions through GRE-zigzag-YZ. 129Xe ventilation defect percent (VDP) was quantified for GRE-zigzag-YZ and bSSFP acquisitions. Relationships and agreement between these VDP measurements were evaluated using Pearson correlation coefficient (r) and Bland-Altman analysis. RESULTS: For 12 HVs, GRE-zigzag-Y and bSSFP required 2.2 s and 10.5 s, respectively, to acquire 129Xe images with a spatial resolution of 3.96 × 3.96 × 10.5 mm3. Structural similarity index, mean absolute error, and Dice similarity coefficient between the two sets of images and ventilated lung regions were 0.85 ± 0.03, 0.0015 ± 0.0001, and 0.91 ± 0.02, respectively. For another 8 HVs and 9 coronavirus disease 2019 subjects, 129Xe images with a nominal spatial resolution of 2.5 × 2.5 × 2.5 mm3 were acquired within 5.5 s per subject using GRE-zigzag-YZ. VDP provided by GRE-zigzag-YZ was strongly correlated (R2 = 0.93, p < 0.0001) with that generated by bSSFP with minimal biases (bias = -0.005%, 95% limit-of-agreement = [-0.414%, 0.424%]). CONCLUSION: Zigzag sampling combined with GRE sequence provides a way for rapid 129Xe ventilation imaging.


Assuntos
COVID-19 , Pulmão , Imageamento por Ressonância Magnética , SARS-CoV-2 , Isótopos de Xenônio , Humanos , COVID-19/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Feminino , Adulto , Pulmão/diagnóstico por imagem , Pessoa de Meia-Idade , Imageamento Tridimensional/métodos , Estudos de Viabilidade
10.
Sci Total Environ ; 935: 173276, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-38796023

RESUMO

Identifying the natural background levels (NBLs), threshold values (TVs), sources and health risks of potentially toxic elements in groundwater is crucial for ensuring the water security of residents in highly urbanized areas. In this study, 96 groundwater samples were collected in urban area of Sichuan Basin, SW China. The concentrations of potentially toxic elements (Li, Fe, Cu, Zn, Al, Pb, B, Ba and Ni) were analyzed for investigating the NBLs, TVs, sources and health risks. The potentially toxic elements followed the concentration order of Fe > Ba > B > Al > Zn > Li > Cu > Ni > Pb. The NBLs and TVs indicated the contamination of potentially toxic elements mainly occurred in the northern and central parts of the study area. The Positive Matrix Factorization (PMF) model identified elevated concentrations of Fe, Al, Li, and B were found to determine groundwater quality. The primary sources of Fe, Al, Pb, and Ni were attributed to the dissolution of oxidation products, with Fe additionally affected by anthropogenic reduction environments. Li and B were determined to be originated from the weathering of tourmaline. High levels of Ni and Cu concentrations were derived from electronic waste leakage, while excessive Ba and Zn were linked to factory emissions and tire wear. The reasonable maximum exposure (RME) of hazard index (HI) was higher than safety standard and reveal the potential health risks in the southwestern study area. Sensitivity analysis demonstrated the Li concentrations possessed the highest weight contributing to health risk. This study provides a valuable information for source-specific risk assessments of potentially toxic elements in groundwater associated with urban areas.


Assuntos
Monitoramento Ambiental , Água Subterrânea , Poluentes Químicos da Água , Água Subterrânea/química , Poluentes Químicos da Água/análise , China , Medição de Risco , Urbanização , Humanos , Metais Pesados/análise , Cidades
11.
Environ Sci Pollut Res Int ; 31(27): 39155-39176, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38809406

RESUMO

An in-depth understanding of nitrate-contaminated surface water and groundwater quality and associated risks is important for groundwater management. Hydrochemical characteristics and driving forces of groundwater quality and non-carcinogenic risks of nitrate were revealed by the integrated approaches of self-organizing map analysis, spatial visualization by geography information system, entropy and irrigation water quality indices, and human health risk model. Groundwater samples were categorized into two clusters by SOM analysis. Cluster I including three samples were Ca-SO4 type and cluster II of remaining 136 samples were Ca-HCO3 type. Hydrochemical compositions of two cluster samples were dominated by water-rock interaction: (1) calcite and gypsum dissolution for cluster I samples and (2) calcite dissolution, silicate weathering, and positive cation exchange for cluster II samples. Nitrate contamination occurred in both cluster I and II samples, primarily induced by agricultural nitrogen fertilizer. The EWQI results showed that 90.97% in total groundwater samples were suitable for drinking purpose, while the IWQI results demonstrated that 65.03% in total groundwater samples were appropriate for irrigation purpose. The HHR model and Monte Carlo simulation indicated that the non-carcinogenic nitrated risk was highest in children. Exposure frequency was the most sensitive factor (86.33% in total) influencing the total non-carcinogenic risk, indicated by sensitivity analysis. Compared with the two clusters of groundwater, surface water has a shorter circulation cycle and lower ion concentrations resulting in better water quality. This study can provide scientific basis for groundwater quality evaluation in other parts of the world.


Assuntos
Irrigação Agrícola , Água Subterrânea , Aprendizado de Máquina , Análise Espacial , Poluentes Químicos da Água , Qualidade da Água , Água Subterrânea/química , Medição de Risco , Poluentes Químicos da Água/análise , Água Potável/química , Humanos , Monitoramento Ambiental/métodos , Nitratos/análise
12.
Artigo em Inglês | MEDLINE | ID: mdl-38747068

RESUMO

BACKGROUND AND AIM: The impact of cholecystectomy, which blocks the cholecystohepatic shunt pathway (CHSP), on the prognosis of patients with hepatocellular carcinoma (HCC) is unclear. Hepatic secondary bile acids (BAs) inhibit natural killer T (NKT) cell-mediated immunity against HCC, and the regulation of homeostasis of hepatic secondary BAs is controlled by the CHSP. However, the influence of CHSP on NKT cell-mediated immunity against HCC remains unclear. METHODS: The clinical data of hospitalized patients undergoing HCC resection were collected. Meanwhile, an in situ HCC mouse model was established, and the CHSP was augmented using oleanolic acid (OA). RESULTS: After 1:1 propensity score matching, Cox regression analysis revealed that cholecystectomy was an independent risk factor for HCC recurrence after hepatectomy (P = 0.027, hazard ratio: 1.599, 95% confidence interval: 1.055-2.422). Experimentally, when OA enhanced CHSP, a significant decrease was observed in the accumulation of secondary BAs in the livers of mice. Additionally, a significant increase was observed in the levels of C-X-C ligand 16 and interferon γ in the serum and tumor tissues. Further, the percentage of C-X-C receptor 6 (+) NKT cells in the tumor tissues increased significantly, and the growth of liver tumors was inhibited. CONCLUSIONS: This clinical study revealed that cholecystectomy promoted the recurrence after radical hepatectomy in patients with HCC. Preserving the normal-functioning gallbladder as much as possible during surgery may be beneficial to the patient's prognosis. Further investigation into the mechanism revealed that CHSP enhanced NKT cell-mediated immunity against HCC by reducing the hepatic accumulation of secondary BAs.

13.
Front Genet ; 15: 1380746, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38798700

RESUMO

The increasing incidence and mortality of prostate cancer worldwide significantly impact the life span of male patients, emphasizing the urgency of understanding its pathogenic mechanism and associated molecular changes that regulate tumor progression for effective prevention and treatment. RNA modification, an important post-transcriptional regulatory process, profoundly influences tumor cell growth and metabolism, shaping cell fate. Over 170 RNA modification methods are known, with prominent research focusing on N6-methyladenosine, N7-methylguanosine, N1-methyladenosine, 5-methylcytidine, pseudouridine, and N4-acetylcytidine modifications. These alterations intricately regulate coding and non-coding RNA post-transcriptionally, affecting the stability of RNA and protein expression levels. This article delves into the latest advancements and challenges associated with various RNA modifications in prostate cancer tumor cells, tumor microenvironment, and core signaling molecule androgen receptors. It aims to provide new research targets and avenues for molecular diagnosis, treatment strategies, and improvement of the prognosis in prostate cancer.

14.
Cells ; 13(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38727294

RESUMO

Information on long-term effects of postovulatory oocyte aging (POA) on offspring is limited. Whether POA affects offspring by causing oxidative stress (OS) and mitochondrial damage is unknown. Here, in vivo-aged (IVA) mouse oocytes were collected 9 h after ovulation, while in vitro-aged (ITA) oocytes were obtained by culturing freshly ovulated oocytes for 9 h in media with low, moderate, or high antioxidant potential. Oocytes were fertilized in vitro and blastocysts transferred to produce F1 offspring. F1 mice were mated with naturally bred mice to generate F2 offspring. Both IVA and the ITA groups in low antioxidant medium showed significantly increased anxiety-like behavior and impaired spatial and fear learning/memory and hippocampal expression of anxiolytic and learning/memory-beneficial genes in both male and female F1 offspring. Furthermore, the aging in both groups increased OS and impaired mitochondrial function in oocytes, blastocysts, and hippocampus of F1 offspring; however, it did not affect the behavior of F2 offspring. It is concluded that POA caused OS and damaged mitochondria in aged oocytes, leading to defects in anxiety-like behavior and learning/memory of F1 offspring. Thus, POA is a crucial factor that causes psychological problems in offspring, and antioxidant measures may be taken to ameliorate the detrimental effects of POA on offspring.


Assuntos
Comportamento Animal , Mitocôndrias , Oócitos , Estresse Oxidativo , Animais , Oócitos/metabolismo , Mitocôndrias/metabolismo , Feminino , Camundongos , Masculino , Ovulação , Ansiedade/metabolismo , Ansiedade/patologia , Antioxidantes/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Blastocisto/metabolismo , Senescência Celular , Memória
15.
iScience ; 27(5): 109722, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38689639

RESUMO

Quantum thermodynamic process involves manipulating and controlling quantum states to extract energy or perform computational tasks with high efficiency. There is still no efficient general method to theoretically quantify the effect of the quantumness of coherence and entanglement in work extraction. In this work, we propose a thermodynamics speed to quantify the extracting work. We show that the coherence of quantum systems can speed up work extracting with respect to some cyclic evolution beyond all incoherent states. We further show the genuine entanglement of quantum systems may speed up work extracting beyond any bi-separable states. This provides a new thermodynamic method to witness entangled systems with physical quantities.

16.
Mol Carcinog ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780126

RESUMO

The therapeutic effect of anlotinib on neuroblastoma is still not fully understood. This study aims to explore the differentiation therapeutic effects of anlotinib on neuroblastoma and its potential association with the neural development regulatory protein collapsin response mediator protein 5 (CRMP5), both in vivo and in vitro. A patient-derived xenograft (PDX) model was established to observe the therapeutic effect of anlotinib. Neuroblastoma cell lines SK-N-SH and SK-N-AS were cultured to observe the morphological impact of anlotinib. Transwell assay was used to evaluate the cell invasion, and Western blot analysis and immunohistochemistry were employed to detect the expressions of neuronal differentiation-related proteins. Results indicate that anlotinib effectively inhibited tumor growth in the PDX model, modulated the expressions of neuronal differentiation markers. In vitro, anlotinib treatment induced neurite outgrowth in neuroblastoma cells and inhibited their invasive ability, reflecting a change in neuronal marker expression patterns consistent with the PDX model. Similarly, in the SK-N-AS mouse xenograft model, anlotinib demonstrated comparable tumor-suppressing effects and promoted neuronal-like differentiation. Additionally, anlotinib significantly downregulated CRMP5 expression in neuroblastoma both in vivo and in vitro. Overexpression of CRMP5 significantly reversed the differentiation therapy effect of anlotinib, exacerbating the aggressiveness and reducing the differentiation level of neuroblastoma. These findings highlight the potential of anlotinib as an anti-neuroblastoma agent. It may suppress tumor proliferation and invasion by promoting the differentiation of tumor cells towards a neuronal-like state, and this differentiation therapy effect involves the inhibition of CRMP5 signaling.

17.
Front Microbiol ; 15: 1378288, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38650871

RESUMO

Fire blight, caused by the Gram-negative bacterium Erwinia amylovora, poses a substantial threat to pome fruit production worldwide. Despite existing control strategies, a pressing need remains for sustainable and environmentally friendly fire blight management. Myxobacteria, renowned for their predatory behavior and potent enzymes, emerge as a groundbreaking biocontrol approach with significant potential. Here, we report the biocontrol potential of a novel Myxococcus fulvus WCH05, against E. amylovora. Using various in vitro and planta assays, we demonstrated the multifaceted biocontrol abilities of strain WCH05. In plate predation assays, strain WCH05 exhibited not only strong predation against E. amylovora but also broad-spectrum activities against other plant pathogenic bacteria. Pre-treatment with strain WCH05 significantly decreased pear blossom blight incidence in detached inflorescence assays, achieving a controlled efficacy of 76.02% that rivaled the antibiotic streptomycin (79.79%). In greenhouse trials, strain WCH05 effectively reduced the wilting rate and disease index in young pear seedlings, exhibiting both protective (73.68%) and curative (68.66%) control. Further investigation revealed that the biocontrol activity of strain WCH05 relies on both direct contact and extracellular enzyme secretion. While cell extracts lacked inhibitory activity, ammonium sulfate-precipitated secreted proteins displayed potent lytic activity against E. amylovora. Substrate spectrum analysis identified peptidases, lipases, and glycosidases among the secreted enzymes, suggesting their potential roles in pathogen degradation and biocontrol efficacy. This study presents the first evidence of Myxococcus fulvus WCH05 as a biocontrol agent against fire blight. Its potent predatory abilities and enzymatic arsenal highlight its potential for sustainable disease management in pome fruit production. Future research will focus on identifying and characterizing specific lytic enzymes and optimizing strain WCH05 application strategies for field efficacy.

18.
Physiol Plant ; 176(2): e14293, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38641970

RESUMO

MicroRNAs (miRNAs) are small noncoding RNAs in eukaryotes. Plant endogenous miRNAs play pivotal roles in regulating plant development and defense responses. MicroRNA394 (miR394) has been reported to regulate plant development, abiotic stresses and defense responses. Previous reports showed that miR394 responded to P. infestans inoculation in potato, indicating that miR394 may be involved in defense responses. In this study, we further investigated its role in potato defense against P. infestans. Stable expression of miR394 in tobacco and potato enhances the susceptibility to P. infestans, which is accompanied with the reduced accumulation of ROS and down-regulation of the PTI (pattern-triggered immunity) marker genes. Besides well-known target StLCR, miR394 also targets StA/N-INVE, which encodes a chloroplast Alkaline/Neutral Invertases (A/N-INVE). Both StLCR and StA/N-INVE positively regulate late blight resistance, while miR394 degrades them. Interestingly, StA/N-INVE is located in the chloroplast, indicating that miR394 may manipulate chloroplast immunity. Degradation of StA/N-INVE may affect the chloroplast function and hence lead to the compromised ROS (reactive oxygen species) burst and reduced retrograde signaling from the chloroplast to the nucleus and cytoplasm. In summary, this study provides new information that miR394 targets and degrades StA/N-INVE and StLCR, which are positive regulators, to enhance potato susceptibility to P. infestans.


Assuntos
MicroRNAs , Phytophthora infestans , Solanum tuberosum , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Phytophthora infestans/genética , Phytophthora infestans/metabolismo , Plantas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Doenças das Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
19.
Sci China Life Sci ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38679667

RESUMO

Engineering disease-resistant plants can be a powerful solution to the issue of food security. However, it requires addressing two fundamental questions: what genes to express and how to control their expressions. To find a solution, we screen CRISPR-edited upstream open reading frame (uORF) variants in rice, aiming to optimize translational control of disease-related genes. By switching uORF types of the 5'-leader from Arabidopsis TBF1, we modulate the ribosome accessibility to the downstream firefly luciferase. We assume that by switching uORF types using CRISPR, we could generate uORF variants with alternative translation efficiency (CRISPR-aTrE-uORF). These variants, capable of boosting translation for resistance-associated genes and dampening it for susceptible ones, can help pinpoint previously unidentified genes with optimal expression levels. To test the assumption, we screened edited uORF variants and found that enhanced translational suppression of the plastic glutamine synthetase 2 can provide broad-spectrum disease resistance in rice with minimal fitness costs. This strategy, which involves modifying uORFs from none to some, or from some to none or different ones, demonstrates how translational agriculture can speed up the development of disease-resistant crops. This is vital for tackling the food security challenges we face due to growing populations and changing climates.

20.
Sci Data ; 11(1): 425, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658632

RESUMO

Near-surface atmospheric moisture is a key environmental and hydro-climatic variable that has significant implications for the natural and human systems. However, high-resolution moisture data are severely lacking for fine-scale studies. Here, we develop the first 1 km high spatial resolution dataset of monthly moisture index collection in China (HiMIC-Monthly) over a long period of 2003~2020. HiMIC-Monthly is generated by the light gradient boosting machine algorithm (LightGBM) based on observations at 2,419 weather stations and multiple covariates, including land surface temperature, vapor pressure, land cover, impervious surface proportion, population density, and topography. This collection includes six commonly used moisture indices, enabling fine-scale assessment of moisture conditions from different perspectives. Results show that the HiMIC-Monthly dataset has a good performance, with R2 values for all six moisture indices exceeding 0.96 and root mean square error and mean absolute error values within a reasonable range. The dataset exhibits high consistency with in situ observations over various spatial and temporal regimes, demonstrating broad applicability and strong reliability.

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