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Glycyl-tRNA synthetase (GARS1) is differentially expressed across cancers. In this study, the value of GARS1 in the diagnosis and prognosis of various cancers was comprehensively evaluated by multiple omics integrative pan-cancer analysis and experimental verification. Through Kaplan-Meier, ROC and multiple databases, we explored GARS1 expression and prognostic and diagnostic patterns across cancers. The GARS1 relative reaction network was identified in PPI, GO, KEGG, methylation models and the genetic mutation atlas. Further research on the GARS1 value in bladder urothelial carcinoma (BLCA) was conducted by regression and nomogram models. We further analyzed the correlation between GARS1 and immune markers and cells in BLCA. Finally, in vitro experiments were used to validate GARS1 the oncogenic function of GARS1 in BLCA. We found that GARS1 was highly expressed across cancers, especially in BLCA. GARS1 expression was correlated with poor survival and had high diagnostic value in most tumor types. GARS1 is significantly associated with tRNA-related pathways whose mutation sites are mainly located on tRNA synthetase. In addition, Upregulation of GARS1 was connected with immune cell infiltration and five key MMR genes. M2 macrophages, TAMs, Th1 and T-cell exhaustion, and marker sets associated with GARS1 expression indicated specific immune infiltration in BLCA. Finally, in vitro experiments validated that GARS1 expression promotes BLCA cell proliferation and metastasis and inhibits apoptosis. Overall, GARS1 can be a novel prognostic and immunological biomarker through multiple omics integrative pan-cancer analysis. The expression of GARS1 in BLCA was positively correlated with specific immune infiltration, indicating that GARS1 might be related to the tumor immune microenvironment.
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Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Biomarcadores de Tumor/genética , Pronóstico , Línea Celular Tumoral , Proliferación Celular/genética , Microambiente Tumoral/inmunología , Microambiente Tumoral/genéticaRESUMEN
Nanolamellar transition metal carbides are gaining increasing attentions because of the promising application in energy storage of their 2D derivatives. There are in-plane and out-of-plane atomic ordered occupations, which is thought to only be formed in separated systems due to totally different origins and crystallographic structure. In present work, starting from (Mo, Nb)4AlC3 o-MAX phase where out-of-plane ordered occupation is experimentally and theoretically proved for Mo/Nb atoms, rare-earth elements (R = Y, Gd-Tm, Lu) are introduced, and the novel Mo3.33- xR0.67NbxAlC3 (x = 1, 1.25, 1.5, 1.75, 2, 2.25, and 2.5) super-ordered (s-) MAX phase is synthesized, where R is ordered at the outer layer in the strict stoichiometry meanwhile Mo/Nb maintains the out-of-plane ordered occupation. By R introduction, s-MAX is easier to be delaminated to obtain the s-MXene with the topochemical ordered vacancies, leading into the enhanced supercapacitance of 114.9 F g-1 in Mo1.33Nb2C3 s-MXene compared with 95.1 F g-1 in Mo2Nb2C3 o-MXene. By Pt anchoring, very low overpotential of 22 mV at a current density of 10 mA cm-2 is achieved for HER applications. This study demonstrates a novel variety of s-MAX phase and seeks to inspire further exploration of the ordered MAX and MXene families.
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Two new family members of mixed alkali-earth metal phosphate and aluminophosphate CaMg(P4O12) and Cs3Al4(PO4)5 were prepared from a phosphate system using a high-temperature solution method. The structural analysis results show that two compounds crystallize in the monoclinic space group C2/c and P21/n and feature a three-dimensional (3D) network. The 3D structure of CaMg(P4O12) consists of [CaO6], [MgO6] octahedra and [P4O12] rings, in which the [MgO6] and [P4O12] rings link to form a 3D structure and Ca2+ cations are filled within the structure. Interestingly, for compound Cs3Al4(PO4)5, its structure features 4, 8, and 12-ring channels with [Al2O4O4P2O4], [Al4O8O8P4O8] and [Al6O12O12P6O12] units as BBUs, respectively; the Cs+ cations are located in the cavities. Furthermore, IR spectral analysis and thermal properties are discussed. UV-vis-NIR diffuse reflectance spectroscopy data show that the UV cutoff edges of CaMg(P4O12) are below 200 nm. Remarkably, in order to determine optical properties and the structure-properties relationship, theoretical calculations were adopted. Electronic structure calculations demonstrate that CaMg(P4O12) has an indirect band gap with the value of 5.86 eV, and Cs3Al4(PO4)5 has a direct band gap of 5.21 eV.
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OBJECTIVE: Most bladder cancers are non-muscle invasive bladder cancer (NMIBC), and transurethral resection of bladder tumors (TURBT) is the standard treatment. However, postoperative recurrence remains a significant challenge, and the influence of bladder tumor location on prognosis is still unclear. This study aims to investigate how tumor location affects the prognosis of NMIBC patients undergoing TURBT and to identify the optimal surgical approach. METHODS: A multicenter study was conducted, which included Chinese NMIBC data from 15 hospitals (1996-2019) and data from 17 registries of the Surveillance, Epidemiology, and End Results database (SEER) (2000-2020). Patients initially diagnosed with NMIBC and undergoing TURBT or partial cystectomy were analyzed, with cases lost to follow-up or with missing data excluded. The study investigated the overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) among patients with different tumor locations. Kaplan-Meier, Cox regression, and propensity score matching methods were employed to explore the association between tumor location and prognosis. Stratified populations were analyzed to minimize bias. RESULTS: This study included 118,477 NMIBC patients and highlighted tumor location as a crucial factor impacting post-TURBT prognosis. Both anterior wall and dome tumors independently predicted adverse outcomes in two cohorts. For anterior wall tumors, the Chinese cohort showed hazard ratios (HR) for OS of 4.35 (P < 0.0001); RFS of 2.21 (P < 0.0001); SEER cohort OS HR of 1.10 (P = 0.0001); DSS HR of 1.13 (P = 0.0183). Dome tumors displayed similar trends (Chinese NMIBC cohort OS HR of 7.91 (P < 0.0001); RFS HR of 2.12 (P < 0.0001); SEER OS HR of 1.05 (P = 0.0087); DSS HR of 1.14 (P = 0.0006)). Partial cystectomy significantly improved the survival of dome tumor patients compared to standard TURBT treatment (P < 0.01). CONCLUSION: This study reveals the significant impact of tumor location in NMIBC patients on the outcomes of TURBT treatment, with tumors in the anterior wall and bladder dome showing poor post-TURBT prognosis. Compared to TURBT treatment, partial cystectomy improves the prognosis for bladder dome tumors. This study provides guidance for personalized treatment and prognosis management for NMIBC patients.
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Rare-earth phosphates were thought to be good candidates as ultraviolet/deep ultraviolet optical materials due to their relatively large bandgap and optical properties. In this paper, the authors screened out a family of XPO4 (X = Sc, Y, La, and Lu) compounds with an enhanced bandgap (HSE06 bandgap ≥ 7.61 eV) and birefringence (0.0934-0.2003@1064 nm) using first-principles calculations. The origin of enhanced optical properties was investigated using projected density of states, distortion indices, and Born effective charges. The results show that the PO4 anionic groups and X-O polyhedra give the main contribution in determining the optical properties, and the PO4 anionic groups give more contribution than other functional basic units. The spin-orbit interaction was also investigated. Similar band structures were found after spin-orbit coupling (SOC) was considered, and slightly enhanced birefringence was found when SOC was applied to these rare-earth phosphates.
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Arylalkylamine N-acetyltransferase (aaNAT) is a crucial enzyme that catalyses the transfer of acetyl groups from acetyl coenzyme A to arylalkylamines and arylamines. Evolutionary studies have identified a distinct class of aaNATs specific to mosquitoes, yet their functions remain elusive. This study focuses on Ae-aaNAT7, a mosquito-unique gene in Aedes aegypti (Diptera:Culicidae), to explore its functionality. Temporal and spatial expression analysis of Ae-aaNAT7 mRNA revealed high expression during embryonic development and in first-instar larvae, with notable expression in the limbs of adult mosquitoes based on tissue expression profiling. By further employing CRISPR/Cas9 technology for loss-of-function studies, our investigation revealed a reduction in the area of white spotting in the limbs of Ae-aaNAT7 mutant adult mosquitoes. Further investigation revealed a significant decrease in the fecundity and hatchability of the mutants. Dissection of the ovaries from Ae-aaNAT7 heterozygous mutants showed a noticeable reduction in the oocyte area compared with wild type. Dissection of the exochorion of the eggs from Ae-aaNAT7 homozygous mutants consistently revealed a striking absence of mature embryos. In addition, RNA interference experiments targeting Ae-aaNAT7 in males resulted in a reduction in fecundity, but no effect on hatchability was observed. These collective insights underscore the substantial impact of Ae-aaNAT7 on reproduction and its pivotal contribution to adult limb pigmentation in Ae. aegypti. These revelations offer insights pivotal for the strategic design of future insecticide targets.
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Purpose: Pancreatic ductal adenocarcinoma (PDAC) is extremely malignant and rapidly progresses. The overall response rate of PDAC to current treatment methods is still unsatisfactory. Thus, identifying novel targets and clarifying the underlying mechanisms associated with PDAC progression may potentially offer additional treatment strategies. AHNAK2 is aberrantly expressed in a variety of tumors and exerts pro-tumorigenic effects. However, the biological role of AHNAK2 in PDAC remains poorly understood. Methods: The expression of AHNAK2 in PDAC and paired non-tumor tissues was detected by immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR). Lentivirus knockdown was performed to investigate the impact of AHNAK2 on the biological function of pancreatic cancer cells. The subcutaneous cell-derived xenograft (CDX) model and the KPC spontaneous mouse model with AHNAK2 silencing were used to observe the effects of AHNAK2 on tumor growth and prognosis. The expression of c-MET at protein level in response to HGF treatment was assessed using western blot. Results: Our results demonstrated that AHNAK2 was highly expressed in PDAC clinical samples and associated with poor prognosis. Knockdown of AHNAK2 significantly inhibited the proliferation, migration, and invasion of pancreatic cancer cells. AHNAK2 knockdown or knockout resulted in tumor growth suppression and prolonged survival in mice with PDAC. In addition, AHNAK2 and c-MET expression levels showed a significant positive correlation at the post-transcriptional level. Mechanistically, AHNAK2 promoted tumor progression by preventing c-MET degradation and persistently activating the HGF/c-MET signaling pathway. Conclusion: Overall, our study revealed that AHNAK2 plays an important role in PDAC progression by modulating the c-MET signaling pathway, and targeting AHNAK2 may be an effective therapeutic strategy for PDAC.
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BACKGROUND: Assessing mechanical properties of the respiratory system (Cst) during mechanical ventilation necessitates an end-inspiration flow of zero, which requires an end-inspiratory occlusion maneuver. This lung model study aimed to observe the effect of airflow obstruction on the accuracy of respiratory mechanical properties during pressure-controlled ventilation (PCV) by analyzing dynamic signals. METHODS: A Hamilton C3 ventilator was attached to a lung simulator that mimics lung mechanics in healthy, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD) models. PCV and volume-controlled ventilation (VCV) were applied with tidal volume (VT) values of 5.0, 7.0, and 10.0 ml/kg. Performance characteristics and respiratory mechanics were assessed and were calibrated by virtual extrapolation using expiratory time constant (RCexp). RESULTS: During PCV ventilation, drive pressure (DP) was significantly increased in the ARDS model. Peak inspiratory flow (PIF) and peak expiratory flow (PEF) gradually declined with increasing severity of airflow obstruction, while DP, end-inspiration flow (EIF), and inspiratory cycling ratio (EIF/PIF%) increased. Similar estimated values of Crs and airway resistance (Raw) during PCV and VCV ventilation were obtained in healthy adult and mild obstructive models, and the calculated errors did not exceed 5%. An underestimation of Crs and an overestimation of Raw were observed in the severe obstruction model. CONCLUSION: Using the modified dynamic signal analysis approach, respiratory system properties (Crs and Raw) could be accurately estimated in patients with non-severe airflow obstruction in the PCV mode.
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Resistencia de las Vías Respiratorias , Enfermedad Pulmonar Obstructiva Crónica , Respiración Artificial , Síndrome de Dificultad Respiratoria , Humanos , Resistencia de las Vías Respiratorias/fisiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Respiración Artificial/métodos , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/fisiopatología , Volumen de Ventilación Pulmonar , Mecánica Respiratoria/fisiología , Pulmón/fisiopatología , Pulmón/fisiología , Rendimiento Pulmonar/fisiología , Modelos Biológicos , AdultoRESUMEN
MicroRNA169 (miR169) has been implicated in multi-stress regulation in annual species such as Arabidopsis, maize and rice. However, there is a lack of experimental functional and mechanistic studies of miR169 in plants, especially in perennial species, and its impact on plant growth and development remains unexplored. Creeping bentgrass (Agrostis stolonifera L.) is a C3 cool-season perennial turfgrass of significant environmental and economic importance. In this study, we generated both miR169 overexpression and knockdown transgenic creeping bentgrass lines. We found that miR169 acts as a positive regulator in abiotic stress responses but is negatively associated with plant growth and development, playing multiple critical roles in the growth and environmental adaptation of creeping bentgrass. These roles include differentiated spatial hormone accumulation patterns associated with growth and stress accommodation, elevated antioxidant activity that alleviates oxidative damage induced by stress, ion-channelling membrane components for maintaining homeostasis under saline conditions, and potential cross-talks with stress-regulating transcription factors such as AsHsfA and AsWRKYs. Our results unravel the role of miR169 in modulating plant development and stress responses in perennial grass species. This underlines the potential of manipulating miR169 to generate crop cultivars with desirable traits to meet diverse agricultural demands.
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Traditional Chinese medicine external prescriptions have displayed excellent clinical effects for treating deep soft tissue injuries. However, the effects cannot be fully utilized due to the limitations of their dosage forms and usage methods. It is still a challenge to develop a satisfactory adjuvant of traditional Chinese medicine external prescriptions. Herein, a hydrogel adjuvant was prepared based on gallic acid coupled ε-poly-l-lysine and partially oxidized hyaluronic acid. The resulting adjuvant shows great physicochemical properties, low hemolysis rate (still much less than 5% at 5 mg/mL), excellent antibacterial ability (about 95% at 2 mg/mL), strong antioxidant ability (1.687 ± 0.085 mmol FeSO4/(g hydrogel) at 1 mg/mL), as well as outstanding biocompatibility. A clinically used Chinese medicine external preparation was selected as an example to investigate the effectiveness of the adjuvant in treating deep soft tissue injuries. The results show that the prescription can be evenly dispersed in the adjuvant. Moreover, the introduction of the prescription has not significantly changed these advanced properties of the adjuvant. Importantly, the hydrogel adjuvant significantly improves the effectiveness of the prescription in treating deep soft tissue injuries. This work offers an alternative approach to the development of a new-type adjuvant of Chinese medicine external preparations and also provides a new strategy for the combination of traditional Chinese medicine and hydrogel to treat clinical diseases.
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Medicamentos Herbarios Chinos , Hidrogeles , Traumatismos de los Tejidos Blandos , Cicatrización de Heridas , Hidrogeles/química , Hidrogeles/farmacología , Hidrogeles/uso terapéutico , Animales , Cicatrización de Heridas/efectos de los fármacos , Traumatismos de los Tejidos Blandos/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Ácido Hialurónico/química , Ácido Hialurónico/uso terapéutico , Ácido Hialurónico/farmacología , Medicina Tradicional China , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antibacterianos/química , Ácido Gálico/química , Ácido Gálico/farmacología , Ácido Gálico/uso terapéutico , Polilisina/química , Polilisina/farmacología , Polilisina/uso terapéutico , Humanos , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Hemólisis/efectos de los fármacos , RatonesRESUMEN
Magnetic skyrmions are promising as next-generation information units. Their antiparticle-the antiskyrmion-has also been discovered in chiral magnets. Here we experimentally demonstrate antiskyrmion sliding in response to a pulsed electric current at room temperature without the requirement of an external magnetic field. This is realized by embedding antiskyrmions in helical stripe domains, which naturally provide one-dimensional straight tracks along which antiskyrmion sliding can be easily launched with low current density and without transverse deflection from the antiskyrmion Hall effect. The higher mobility of the antiskyrmions in the background of helical stripes in contrast to the typical ferromagnetic state is a result of intrinsic material parameters and elastic energy of the stripe domain, thereby smearing out the random pinning potential, as supported by micromagnetic simulations. The demonstration and comprehensive understanding of antiskyrmion movement along naturally straight tracks offers a new perspective for (anti)skyrmion application in spintronics.
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To achieve the collaborative elimination of N2O and carbon of potent greenhouse pollutants from automotive mobile sources, a chemical kinetic model is developed to accurately track the heterogeneous process of carbon-catalyzed N2O reduction based on density functional theory, with experimental data used to validate the model's reliability. The influence of carbon structure, site density, and surface chemical properties on N2O catalytic reduction can be analyzed within this system. Results reveal that the free-edge site of carbon accurately describes the catalytic reduction process of N2O. Adsorption of N2O to carbon edges in O-down, N-down, or parallel orientations exhibits an exothermic process with energy barriers. The N2O with O-down reduction pathway predominates due to the limitations imposed by the unitary carbon site. As the number of active carbon atoms at carbon edges increases, the N2O reaction mode tends towards parallel and N-down pathways, resulting in a significant enhancement of N2O conversion rates and a reduction in catalytic temperatures, with the lowest achievable temperature being 300 K. Furthermore, the triplet carbon structure exhibits higher efficiency in N2O catalytic reduction compared to the singlet carbon structure, achieving a remarkable N2O conversion rate of 93.8 % within the typical temperature exhaust window of diesel engines. This study supplies a breakthrough for carbon materials as catalysts for achieving high N2O conversion rates at low cost, which is important for the collaborative catalytic elimination of N2O and carbon black pollutants.
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Two deep ultraviolet (DUV) hydroxylated-alkali-metal borates, NaRbB10O14(OH)4 (I) and Na3CsB10O16(OH)2 (II), have been successfully synthesized by a high-temperature solution and solvothermal method. Both of them feature [B5Om(OH)n] units, which form chains for (I) and bilayers with nine-membered boron rings for (II). It is worth noting that both compounds exhibit very wide theoretical band gaps of 7.33 and 6.55 eV for (I) and (II), respectively, which denotes that they should have desirable DUV transmittance ability. Moreover, the title compounds have moderate birefringence owing to the π-conjugated [BO3], [BO2(OH)] groups, corresponding to 0.070 for (I) and 0.054 for (II) at 1064 nm. The structure characteristics and optical properties were also investigated and discussed. The results make it beneficial for exploring novel DUV hydroxylated borate optical crystals.
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This study investigated the function of the MDR49 gene in Aedes aegypti. MDR49 mutants were constructed using CRISPR/Cas9 technology; the mutation led to increased sensitivity to ivermectin (LC50: from 1.3090 mg L-1 to 0.5904 mg L-1), and a reduction in midgut trypsin activity. These findings suggest that the P-gp encoded by MDR49 confers resistance to ivermectin and impacts the reproductive function in Ae. aegypti. RNA interference technology showed that knockdown of MDR49 gene resulted in a significant decrease in the expression of VGA1 after a blood meal, as well as a decrease in the number of eggs laid and their hatching rate. LC-MS revealed that following ivermectin treatment, the MDR493d+2s/3d+2s strain larvae exhibited significantly higher drug concentrations in the head and fat body compared to the wild type. Modeling of inward-facing P-gp and molecular docking found almost no difference in the affinity of P-gp for ivermectin before and after the mutation. However, modeling of the outward-facing conformation demonstrated that the flexible linker loop between TM5 and TM6 of P-gp undergoes changes after the mutation, resulting in a decrease in trypsin activity and an increase in sensitivity to ivermectin. These results provide useful insights into ivermectin resistance and the other roles played by the MDR49 gene.
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Aedes , Proteínas de Insectos , Ivermectina , Animales , Aedes/efectos de los fármacos , Aedes/genética , Aedes/metabolismo , Ivermectina/farmacología , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Tripsina/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Fertilidad/efectos de los fármacos , Resistencia a los Insecticidas/genética , Inhibidores de Tripsina/metabolismo , Inhibidores de Tripsina/farmacología , Simulación del Acoplamiento Molecular , Insecticidas/farmacologíaRESUMEN
Objective: Pancreatic carcinoma is characterised by high aggressiveness and a bleak prognosis; optimising related treatment decisions depends on the availability of reliable prognostic markers. This study was designed to compare various blood biomarkers, such as neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), platelet/lymphocyte ratio (PLR), C-reactive protein (CRP), albumin (Alb), plasma fibrinogen (PF), and CRP/Alb in patients with pancreatic carcinoma. Methods: Our study retrospectively reviewed 250 patients with pancreatic carcinoma diagnosed between July 2007 and December 2018. The Cutoff Finder application was used to calculate the optimal values of CRP/Alb and PF. The Chi-square test or Fisher's exact test was used to analyse the correlation of CRP/Alb and PF with other clinicopathological factors. Conducting univariate and multivariate analyses allowed further survival analysis of these prognostic factors. Results: Multivariate analysis revealed that, in a cohort of 232 patients with pancreatic ductal adenocarcinoma (PDAC), the PF level exhibited statistical significance for overall survival (hazard ratio (HR) = 0.464; p = 0.023); however, this correlation was not found in the entire group of 250 patients with pancreatic carcinoma. Contrastingly, the CRP/Alb ratio was demonstrated statistical significance in both the entire pancreatic carcinoma cohort (HR = 0.471; p = 0.026) and the PDAC subgroup (HR = 0.484; p = 0.034). CRP/Alb and PF demonstrated a positive association (r=0.489, p<0.001) as indicated by Spearman's rank correlation analysis. Additionally, in 232 PDAC patients, the combination of the CRP/Alb ratio and PF had synergistic effects on prognosis when compared with either the CRP/Alb ratio or the PF concentration alone. Conclusion: PF concentration is a convenient, rapid, and noninvasive biomarker, and its combination with the CRP/Alb ratio could significantly enhance the accuracy of prognosis prediction in pancreatic carcinoma patients, especially those with the most common histological subtype of PDAC.
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This paper reports an innovative study that aims to address key issues in the efficient recycling of wastepaper cellulose. The research team utilized the temperature-responsive upper critical solution temperature (UCST) polymer P(NAGA-b-DMA) in combination with the LytA label's affinity for choline analogs. This innovative approach enabled them to successfully develop a novel soluble immobilized enzyme, P(NAGA-b-DMA)-cellulase. This new enzyme has proven highly effective, significantly enhancing the degradation of wastepaper cellulose while demonstrating exceptional stability. Compared with the traditional insoluble immobilized cellulase, the enzyme showed a significant improvement in the pH, temperature stability, recycling ability, and storage stability. A kinetic parameter calculation showed that the enzymatic effectiveness of the soluble immobilized enzyme was much better than that of the traditional insoluble immobilized cellulase. After the immobilization reaction, the Michaelis constant of the immobilized enzyme was only increased by 11.5%. In the actual wastepaper degradation experiment, the immobilized enzyme was effectively used, and it was found that the degradation efficiency of wastepaper cellulose reached 80% of that observed in laboratory conditions. This novel, thermosensitive soluble immobilized cellulase can efficiently catalyze the conversion of wastepaper cellulose into glucose under suitable conditions, so as to further ferment into environmentally friendly biofuel ethanol, which provides a solution to solve the shortage of raw materials and environmental protection problems in the paper products industry.
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Celulasa , Enzimas Inmovilizadas , Enzimas Inmovilizadas/metabolismo , Celulosa/metabolismo , Celulasa/metabolismo , Temperatura , Polímeros , HidrólisisRESUMEN
BACKGROUND: Intensive swine breeding industry generates a complex environment where several microbial interactions occur and which constitutes a challenge for biosafety. Ad libitum feeding strategies and low levels of management contribute to residual and wasted feed for lactating sows, which provides a source of nutrients and microbial source for houseflies in warm climates. Due to the absence of the all-in/all-out system, the coexistence of sows of two production stages including gestating and lactating sows in the farrowing barn may have potential negative impacts. In this research, we evaluated the effects of lactating sow leftover on the environmental microbiota of the farrowing barn and the contribution of microbial environments to the gestating sow fecal bacterial structure with a 30-day-long treatment of timely removing lactating residual feed. RESULTS: Houseflies in the farrowing barn mediate the transmission of microorganisms from lactating sow leftover to multiple regions. Leuconostoc, Weissella, Lactobacillus and Pediococcus from the leftover which can produce exopolysaccharides, are more capable of environmental transmission than pathogenic microorganisms including Staphylococcus and Streptococcus and utilize houseflies to achieve spread in environmental regions of the farrowing barn. Leftover removal treatment blocked the microbial transmission chain mediated by houseflies, downregulated the relative abundance of pathogenic bacteria including Escherichia-Shigella and Streptococcus among houseflies, environmental regions and fecal bacteria of gestating sows in the farrowing barn and effectively attenuate the increment of Weissella and RF39 relative abundance in gestating sow feces due to the presence of lactating sows. CONCLUSIONS: Lactating sow leftover is a non-negligible microbial contributor of environment in farrowing barn whose transmission is mediated by houseflies. A 30-day-long treatment of removing lactating sow residual feed cause significant changes in the microbial structure of multiple environmental regions within the farrowing barn via altering the microbiota carried by houseflies. Meanwhile, lactating sow leftover affect the fecal microbial structure of gestating sows in the same farrowing barn, while removal of lactating sow leftover alleviates the contribution of microbial transmission.
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Volatile sulfur compounds, such as dimethyl sulfide (DMS), carbonyl sulfide (OCS), and carbon disulfide (CS2), have significant implications for both atmospheric chemistry and climate change. Despite the crucial role of oceans in regulating their atmospheric budgets, our comprehension of their cycles in seawater remains insufficient. To address this gap, a field investigation was conducted in the western North Pacific to clarify the sources, sinks, and biogeochemical controls of these gases in two different marine environments, including relatively eutrophic Kuroshio-Oyashio extension (KOE) and oligotrophic North Pacific subtropical gyre. Our findings revealed higher concentrations of these gases in both seawater and the atmosphere in the KOE compared to the subtropical gyre. In the KOE, nutrient-rich upwelling stimulated rapid DMS biological production, while reduced seawater temperatures hindered the removal of OCS and CS2, leading to their accumulation. Furthermore, we have quantitatively evaluated the relative contribution of each pathway to the source and sink of DMS, OCS, and CS2 within the mixed layer and identified vertical exchange as a potential sink in most cases, transporting substantial amounts of these gases from the mixed layer to deeper waters. This research advances our understanding of sulfur gas source-sink dynamics in seawater, contributing to the assessment of their marine emissions and atmospheric budgets.
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Submesoscale fronts, with horizontal scale of 0.1-10 km, are key components of climate system by driving intense vertical transports of heat, salt and nutrients in the ocean. However, our knowledge on how large the vertical transport driven by one single submesoscale front can reach remains limited due to the lack of comprehensive field observations. Here, based on high-resolution in situ observations in the Kuroshio-Oyashio Extension region, we detect an exceptionally sharp submesoscale front. The oceanic temperature (salinity) changes sharply from 14 °C (34.55 psu) to 2 °C (32.7 psu) within 2 km across the front from south to north. Analysis reveals intense vertical velocities near the front reaching 170 m day-1, along with upward heat transport up to 1.4 × 10-2 °C m s-1 and salinity transport reaching 4 × 10-4 psu m s-1. The observed heat transport is much larger than the values reported in previous observations and is three times as that derived from current eddy-rich climate models, whereas the salinity transport enhances the nutrients concentration with prominent implications for marine ecosystem and fishery production. These observations highlight the vertical transport of submesoscale fronts and call for a proper representation of submesoscale processes in the next generation of climate models.
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Clear cell renal cell carcinoma (ccRCC) is a complex disease with remarkable immune and metabolic heterogeneity. Here we perform genomic, transcriptomic, proteomic, metabolomic and spatial transcriptomic and metabolomic analyses on 100 patients with ccRCC from the Tongji Hospital RCC (TJ-RCC) cohort. Our analysis identifies four ccRCC subtypes including De-clear cell differentiated (DCCD)-ccRCC, a subtype with distinctive metabolic features. DCCD cancer cells are characterized by fewer lipid droplets, reduced metabolic activity, enhanced nutrient uptake capability and a high proliferation rate, leading to poor prognosis. Using single-cell and spatial trajectory analysis, we demonstrate that DCCD is a common mode of ccRCC progression. Even among stage I patients, DCCD is associated with worse outcomes and higher recurrence rate, suggesting that it cannot be cured by nephrectomy alone. Our study also suggests a treatment strategy based on subtype-specific immune cell infiltration that could guide the clinical management of ccRCC.