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1.
Artículo en Inglés | MEDLINE | ID: mdl-38747068

RESUMEN

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.

2.
Magn Reson Med ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38770624

RESUMEN

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.

3.
Cells ; 13(9)2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38727294

RESUMEN

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.


Asunto(s)
Conducta Animal , Mitocondrias , Oocitos , Estrés Oxidativo , Animales , Oocitos/metabolismo , Mitocondrias/metabolismo , Femenino , Ratones , Masculino , Ovulación , Ansiedad/metabolismo , Ansiedad/patología , Antioxidantes/metabolismo , Hipocampo/metabolismo , Hipocampo/patología , Blastocisto/metabolismo , Senescencia Celular , Memoria
4.
iScience ; 27(5): 109722, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38689639

RESUMEN

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.

5.
Mycology ; 15(1): 17-29, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38558845

RESUMEN

Colorectal cancer (CRC) is a prevalent tumour with high morbidity rates worldwide, and its incidence among younger populations is rising. Early diagnosis of CRC can help control the associated mortality. Fungi are common microorganisms in nature. Recent studies have shown that fungi may have a similar association with tumours as bacteria do. As an increasing number of tumour-associated fungi are discovered, this provides new ideas for the diagnosis and prognosis of tumours. The relationship between fungi and colorectal tumours has also been recently identified by scientists. Therefore, this paper describes the limitations and prospects of the application of fungi in diagnosing CRC and predicting CRC prognosis.

6.
World J Clin Cases ; 12(9): 1560-1568, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38576738

RESUMEN

BACKGROUND: Unicompartmental knee arthroplasty (UKA) has great advantages in the treatment of unicompartmental knee osteoarthritis, but its revision rate is higher than that of total knee arthroplasty. AIM: To summarize and analyse the causes of revision after UKA. METHODS: This is a retrospective case series study in which the reasons for the first revision after UKA are summarized. We analysed the clinical symptoms, medical histories, laboratory test results, imaging examination results and treatment processes of the patients who underwent revision and summarized the reasons for primary revision after UKA. RESULTS: A total of 13 patients, including 3 males and 10 females, underwent revision surgery after UKA. The average age of the included patients was 67.62 years. The prosthesis was used for 3 d to 72 months. The main reasons for revision after UKA were improper suturing of the surgical opening (1 patient), osteophytes (2 patients), intra-articular loose bodies (2 patients), tibial prosthesis loosening (2 patients), rheumatoid arthritis (1 patient), gasket dislocation (3 patients), anterior cruciate ligament injury (1 patient), and medial collateral ligament injury with residual bone cement (1 patient). CONCLUSION: The causes of primary revision after UKA were gasket dislocation, osteophytes, intra-articular loose bodies and tibial prosthesis loosening. Avoidance of these factors may greatly reduce the rate of revision after UKA, improve patient satisfaction and reduce medical burden.

7.
World J Clin Cases ; 12(8): 1454-1460, 2024 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-38576808

RESUMEN

BACKGROUND: A rare autosomal recessive genetic disorder, 3M syndrome, is characterized by severe intrauterine and postnatal growth retardation. Children with 3M syndrome typically exhibit short stature, facial deformities, long tubular bones, and high vertebral bodies but generally lack mental abnormalities or other organ damage. Pathogenic genes associated with 3M syndrome include CUL7, OBSL1 and CCDC8. The clinical and molecular characteristics of patient with 3M syndrome are unique and serve as important diagnostic indicators. CASE SUMMARY: In this case, the patient displayed square shoulders, scoliosis, long slender tubular bones, and normal neurological development. Notably, the patient did not exhibit the typical dysmorphic facial features, relative macrocephaly, or growth retardation commonly observed in individuals with 3M syndrome. Whole exon sequencing revealed a novel heterozygous c.56681+1G>C (Splice-3) variant and a previously reported nonsense heterozygous c.3341G>A (p.Trp1114Ter) variant of OBSL1. Therefore, it is important to note that the clinical features of 3M syndrome may not always be observable, and genetic confirmation is often required. Additionally, the identification of the c.5683+1G>C variant in OBSL1 is noteworthy because it has not been previously reported in public databases. CONCLUSION: Our study identified a new variant (c.5683+1G>C) of OBSL1 that contributes to expanding the molecular profile of 3M syndrome.

8.
Physiol Plant ; 176(2): e14293, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38641970

RESUMEN

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.


Asunto(s)
MicroARNs , Phytophthora infestans , Solanum tuberosum , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Phytophthora infestans/genética , Phytophthora infestans/metabolismo , Plantas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Enfermedades de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas
9.
Viruses ; 16(4)2024 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-38675852

RESUMEN

Fire blight, caused by the bacterium Erwinia amylovora, is a major threat to pear production worldwide. Bacteriophages, viruses that infect bacteria, are a promising alternative to antibiotics for controlling fire blight. In this study, we isolated a novel bacteriophage, RH-42-1, from Xinjiang, China. We characterized its biological properties, including host range, plaque morphology, infection dynamics, stability, and sensitivity to various chemicals. RH-42-1 infected several E. amylovora strains but not all. It produced clear, uniform plaques and exhibited optimal infectivity at a multiplicity of infection (MOI) of 1, reaching a high titer of 9.6 × 109 plaque-forming units (PFU)/mL. The bacteriophage had a short latent period (10 min), a burst size of 207 PFU/cell, and followed a sigmoidal one-step growth curve. It was stable at temperatures up to 60 °C but declined rapidly at higher temperatures. RH-42-1 remained viable within a pH range of 5 to 9 and was sensitive to extreme pH values. The bacteriophage demonstrates sustained activity upon exposure to ultraviolet radiation for 60 min, albeit with a marginal reduction. In our assays, it exhibited a certain level of resistance to 5% chloroform (CHCl3), 5% isopropanol (C3H8O), and 3% hydrogen peroxide (H2O2), which had little effect on its activity, whereas it showed sensitivity to 75% ethanol (C2H5OH). Electron microscopy revealed that RH-42-1 has a tadpole-shaped morphology. Its genome size is 14,942 bp with a GC content of 48.19%. Based on these characteristics, RH-42-1 was identified as a member of the Tectiviridae family, Alphatectivirus genus. This is the first report of a bacteriophage in this genus with activity against E. amylovora.


Asunto(s)
Bacteriófagos , Erwinia amylovora , Microbiología del Suelo , Bacteriófagos/aislamiento & purificación , Bacteriófagos/genética , Bacteriófagos/fisiología , Bacteriófagos/clasificación , China , Erwinia amylovora/virología , Erwinia amylovora/efectos de los fármacos , Genoma Viral , Especificidad del Huésped , Concentración de Iones de Hidrógeno , Filogenia , Enfermedades de las Plantas/microbiología , Pyrus/microbiología , Pyrus/virología
10.
Int J Biol Macromol ; 267(Pt 1): 131323, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38574912

RESUMEN

Sphingolipids serve as essential components of biomembrane and possess significant bioactive properties. Sphingosine-1-phophate (S1P) plays a key role in plant resistance to stress, but its specific impact on plant growth and development remains to be fully elucidated. Cotton fiber cells are an ideal material for investigating the growth and maturation of plant cells. In this study, we examined the content and composition of sphingosine (Sph) and S1P throughout the progression of fiber cell development. The content of S1P elevated gradually during fiber elongation but declined during the transition stage. Exogenous application of S1P promoted fiber elongation while using of FTY720 (an antagonist of S1P), and DMS (an inhibitor of LCBK) hindered fiber elongation. Cotton Long Chain Base Kinase 1 (GhLCBK1) was notably expressed during the fiber elongation stage, containing all conserved domains of LCBK protein and localized in the endoplasmic reticulum. Overexpression GhLCBK1 increased the S1P content and promoted fiber elongation while retarded secondary cell wall (SCW) deposition. Conversely, downregulation of GhLCBK1 reduced the S1P levels, and suppressed fiber elongation, and accelerated SCW deposition. Transcriptome analysis revealed that upregulating GhLCBK1 or applying S1P induced the expression of GhEXPANSIN and auxin related genes. Furthermore, the levels of IAA were elevated and reduced in the fibers when up-regulating or down-regulating GhLCBK1, respectively. Our investigation demonstrated that GhLCBK1 and its product S1P facilitated the elongation of fiber cells by affecting auxin biosynthesis. This study contributes novel insights into the intricate regulatory pathways involved in fiber cell elongation, identifying GhLCBK1 as a potential target gene and laying the groundwork for enhancing fiber quality via genetic manipulation.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Gossypium , Ácidos Indolacéticos , Lisofosfolípidos , Fosfotransferasas (Aceptor de Grupo Alcohol) , Esfingosina , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Gossypium/genética , Gossypium/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Ácidos Indolacéticos/metabolismo , Ácidos Indolacéticos/farmacología , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Lisofosfolípidos/metabolismo , Fibra de Algodón , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Pared Celular/metabolismo , Pared Celular/efectos de los fármacos
11.
Front Microbiol ; 15: 1378288, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38650871

RESUMEN

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.

12.
Sci Data ; 11(1): 425, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38658632

RESUMEN

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.

13.
BMC Anesthesiol ; 24(1): 130, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38580909

RESUMEN

BACKGROUND: Skin mottling is a common manifestation of peripheral tissue hypoperfusion, and its severity can be described using the skin mottling score (SMS). This study aims to evaluate the value of the SMS in detecting peripheral tissue hypoperfusion in critically ill patients following cardiac surgery. METHODS: Critically ill patients following cardiac surgery with risk factors for tissue hypoperfusion were enrolled (n = 373). Among these overall patients, we further defined a hypotension population (n = 178) and a shock population (n = 51). Hemodynamic and perfusion parameters were recorded. The primary outcome was peripheral hypoperfusion, defined as significant prolonged capillary refill time (CRT, > 3.0 s). The characteristics and hospital mortality of patients with and without skin mottling were compared. The area under receiver operating characteristic curves (AUROC) were used to assess the accuracy of SMS in detecting peripheral hypoperfusion. Besides, the relationships between SMS and conventional hemodynamic and perfusion parameters were investigated, and the factors most associated with the presence of skin mottling were identified. RESULTS: Of the 373-case overall population, 13 (3.5%) patients exhibited skin mottling, with SMS ranging from 1 to 5 (5, 1, 2, 2, and 3 cases, respectively). Patients with mottling had lower mean arterial pressure, higher vasopressor dose, less urine output (UO), higher CRT, lactate levels and hospital mortality (84.6% vs. 12.2%, p < 0.001). The occurrences of skin mottling were higher in hypotension population and shock population, reaching 5.6% and 15.7%, respectively. The AUROC for SMS to identify peripheral hypoperfusion was 0.64, 0.68, and 0.81 in the overall, hypotension, and shock populations, respectively. The optimal SMS threshold was 1, which corresponded to specificities of 98, 97 and 91 and sensitivities of 29, 38 and 67 in the three populations (overall, hypotension and shock). The correlation of UO, lactate, CRT and vasopressor dose with SMS was significant, among them, UO and CRT were identified as two major factors associated with the presence of skin mottling. CONCLUSION: In critically ill patients following cardiac surgery, SMS is a very specific yet less sensitive parameter for detecting peripheral tissue hypoperfusion.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Hipotensión , Choque Séptico , Humanos , Enfermedad Crítica , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Hipotensión/diagnóstico , Hipotensión/complicaciones , Lactatos
14.
Sci China Life Sci ; 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38679667

RESUMEN

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.

15.
Sci Adv ; 10(13): eadl1598, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38552023

RESUMEN

Heatwaves are consecutive hot days with devastating impacts on human health and the environment. These events may evolve across both space and time, characterizing a spatiotemporally contiguous propagation pattern that has not been fully understood. Here, we track the spatiotemporally contiguous heatwaves in both reanalysis datasets and model simulations and examine their moving patterns (i.e., moving distance, speed, and direction) in different continents and periods. Substantial changes in contiguous heatwaves have been identified from 1979 to 2020, with longer persistence, longer traveling distance, and slower propagation. These changes have been amplified since 1997, probably due to the weakening of eddy kinetic energy, zonal wind, and anthropogenic forcing. The results suggest that longer-lived, longer-traveling, and slower-moving contiguous heatwaves will cause more devastating impacts on human health and the environment in the future if greenhouse gas emissions keep rising and no effective measures are taken immediately. Our findings provide important implications for the adaption and mitigation of globally connected extreme heatwaves.

16.
Aging (Albany NY) ; 16(6): 5526-5544, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38517383

RESUMEN

Ubiquitin-specific protease 36 (USP36) has been reported to exhibit oncogenic effects in various malignancies, but the function of USP36 in colon cancer progression remains indefinite. Herein, we aimed to determine the role and mechanism of USP36 in malignant phenotypes of colon cancer cells and explore the potential drug targeting USP36. Bioinformatics analyses indicated that USP36 is highly expressed and significantly related to tumor stages in colon cancer. Besides, USP36 was further up-regulated in oxaliplatin (Oxa)-resistant colon cancer cells. Colony formation, Edu staining, Transwell, wound healing, sphere formation, and CCK-8 assays were conducted and showed that the proliferation, Oxa-resistance, migration, stemness, and invasion of HCT116 cells were promoted after overexpressing USP36, while suppressed by USP36 knockdown. Mechanically, USP36 enhances c-Myc protein stabilization in HCT116 cells via deubiquitination. AutoDock tool and ubiquitin-AMC hydrolysis assay identified cinobufotalin (CBF), an anti-tumor drug, maybe a USP36 inhibitor by inhibiting its deubiquitination activity. CBF significantly prohibited proliferation, migration, invasion, and stemness of HCT116 cells and reversed Oxa-resistance, whereas enforced expression of USP36 blocked these effects. Moreover, in vivo analyses confirmed the oncogenic role of USP36 and the therapeutic potential of CBF in the malignancy of colon cancer. In conclusion, CBF may be a promising therapeutic agent for colon cancer due to its regulation of the USP36/c-Myc axis.


Asunto(s)
Bufanólidos , Neoplasias del Colon , Ubiquitina Tiolesterasa , Humanos , Ubiquitina Tiolesterasa/genética , Ubiquitina Tiolesterasa/metabolismo , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Línea Celular Tumoral , Células HeLa , Proliferación Celular
17.
ACS Synth Biol ; 13(5): 1492-1497, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38525720

RESUMEN

Ruminant livestock produce around 24% of global anthropogenic methane emissions. Methanogenesis in the animal rumen is significantly inhibited by bromoform, which is abundant in seaweeds of the genus Asparagopsis. This has prompted the development of livestock feed additives based on Asparagopsis to mitigate methane emissions, although this approach alone is unlikely to satisfy global demand. Here we engineer a non-native biosynthesis pathway to produce bromoform in vivo with yeast as an alternative biological source that may enable sustainable, scalable production of bromoform by fermentation. ß-dicarbonyl compounds with low pKa values were identified as essential substrates for bromoform production and enabled bromoform synthesis in engineered Saccharomyces cerevisiae expressing a vanadate-dependent haloperoxidase gene. In addition to providing a potential route to the sustainable biological production of bromoform at scale, this work advances the development of novel microbial biosynthetic pathways for halogenation.


Asunto(s)
Ingeniería Metabólica , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Ingeniería Metabólica/métodos , Vías Biosintéticas/genética , Animales , Fermentación , Metano/metabolismo , Metano/biosíntesis , Algas Marinas/metabolismo , Algas Marinas/genética , Halogenación
18.
Br J Haematol ; 204(5): 1999-2006, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38438264

RESUMEN

Prolonged coagulation times, such as activated partial thromboplastin time (APTT) and thrombin time (TT), are common in patients infected with severe fever with thrombocytopenia syndrome virus (SFTSV) and have been confirmed to be related to patient's poor outcome by previous studies. To find out the reason for prolonged coagulation time in patients with SFTSV infection, and whether it predicts haemorrhagic risk or not. Seventy-eight consecutive patients with confirmed SFTSV infection were enrolled in this prospective, single-centre, observational study. Several global and specific coagulation parameters of these patients on admission were detected, and the haemorrhagic events during hospitalization and their outcomes were recorded. Most of the enrolled patients had prolonged APTT (82.1%) and TT (80.8%), normal prothrombin time (83.3%) and intrinsic coagulation factors above haemostatic levels (97.4%). The heparin-like effect was confirmed by a protamine neutralization test and anti-Xa activity detection in most patients. Interestingly, the APTT and TT results were significantly positively correlated with the levels of endothelial markers and viral load, respectively. The APTT was independently associated with the haemorrhage of patients. The prolonged APTT and TT of SFTS patients may mainly be attributed to endogenous heparinoids and are associated with increased haemorrhagic risk.


Asunto(s)
Hemorragia , Síndrome de Trombocitopenia Febril Grave , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Tiempo de Tromboplastina Parcial , Hemorragia/sangre , Hemorragia/etiología , Estudios Prospectivos , Síndrome de Trombocitopenia Febril Grave/sangre , Heparina/uso terapéutico , Adulto , Tiempo de Trombina , Phlebovirus , Coagulación Sanguínea , Factores de Riesgo , Anciano de 80 o más Años
19.
Theriogenology ; 220: 84-95, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38490113

RESUMEN

Understanding the mechanisms for oocyte maturation and optimizing the protocols for in vitro maturation (IVM) are greatly important for improving developmental potential of IVM oocytes. The miRNAs expressed in cumulus cells (CCs) play important roles in oocyte maturation and may be used as markers for selection of competent oocytes/embryos. Although a recent study from our group identified several new CCs-expressed miRNAs that regulate cumulus expansion (CE) and CC apoptosis (CCA) in mouse oocytes, validation of these findings and further investigation of mechanisms of action in other model species was essential before wider applications. By using both in vitro and in vivo pig oocyte models with significant differences in CE, CCA and developmental potential, the present study validated that miR-149 and miR-31 improved CE and developmental potential while suppressing CCA of pig oocytes. We demonstrated that miR-149 and miR-31 targeted SMAD family member 6 (SMAD6) and transforming growth factor ß2 (TGFB2), respectively, in the transforming growth factor-ß (TGF-ß) signaling. Furthermore, both miR-149 and miR-31 increased CE and decreased CCA via activating SMAD family member 2 (SMAD2) and increasing the expression of SMAD2 and SMAD family member 4. In conclusion, the present results show that miR-149 and miR-31 improved CE and developmental potential while suppressing CCA of pig oocytes by activating the TGF-ß signaling, suggesting that they might be used as markers for pig oocyte quality.


Asunto(s)
Células del Cúmulo , Técnicas de Maduración In Vitro de los Oocitos , MicroARNs , Oocitos , Animales , Femenino , Células del Cúmulo/fisiología , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Técnicas de Maduración In Vitro de los Oocitos/métodos , MicroARNs/genética , MicroARNs/metabolismo , Oocitos/fisiología , Porcinos , Factor de Crecimiento Transformador beta/farmacología , Factor de Crecimiento Transformador beta/metabolismo
20.
Opt Express ; 32(4): 5500-5514, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38439275

RESUMEN

We present a 4×4 real-valued channel equalizer with embedded phase estimator, designed for carrier phase and frequency offset estimation and compensation in coherent optical communications with in-phase/quadrature (IQ) impairments. These impairments include IQ timing skew, gain imbalance, and quadrature phase errors at the transmitter side. To achieve adaptive control of the equalizer's filter coefficients, we employ the decision-directed least mean square (DD-LMS) algorithm. This algorithm minimizes the error between the filter outputs and the desired signals in a symbol-by-symbol manner, resulting in faster channel coefficients adaptation speed. Simulation results for a 60 GBaud polarization-multiplexing 16 quadrature amplitude modulation (PM-16QAM) signal demonstrate that our proposed equalizer outperforms a 2×2 cascaded multi modulus algorithm-based (CMMA-based) equalizer, a 2×2 complex-valued method based on the DD-LMS algorithm, and the 4×4 real-valued equalizer without embedded frequency offset estimation (FOE), when the transmitter IQ impairments exist. Experimental validation is also conducted for the 60 GBaud PM-16QAM and 45 GBaud PM-64QAM signals. Similar to the simulation results, our experiments show that the proposed 4×4 real-valued equalizer with embedded FOE can achieve effective SNR penalties of less than 0.41 dB at 7 ps skew, 1.33 dB at 3.5 dB gain imbalance, and 1.64 dB at the bias voltage shift of 0.5 V for the 60 GBaud PM-16QAM signal. Finally, our experimental results confirm the effectiveness of our proposed method in carrier phase estimation as well as the frequency offset compensation, when compared with 4×4 real-valued equalizer without embedded FOE.

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