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Objective: To compare the clinical effects of neoadjuvant chemoradiotherapy (NCRT) and neoadjuvant chemotherapy (NCT) on complications and recurrence in patients with advanced gastric cancer (AGC). Method: This was a retrospective study. A total of 83 patients with AGC admitted to Chengde Central Hospital between Jan. 2019 and Jun. 2021 were selected and divided into the observation group(n=41) and the control group(n=42) using a random number table. Patients in the control group received XELOX chemotherapy, and those in the observation group received intensity-modulated radiotherapy (IMRT) with concurrent XELOX chemotherapy. Compared efficacy, pathological complete response rate (pCR), R0 resection rate, adverse reactions, and quality of life (QOL) before and after treatment between the two groups. Results: The efficacy, pCR, and R0 resection rate of the observation group were significantly increased compared with those of the control group. Comparison of complications showed the number of patients experiencing gastrointestinal (GI) reactions, increased BUN, increased GPT, alopecia, and pigmentation in the observation group was decreased compared with that in the control group, with no statistically significant differences(p>0.05), and the number of patients experiencing myelosuppression was statistically significant between the two groups(p<0.05). There were no significant differences in sub-scores of physical, role, emotional, cognitive, and social functions and the overall score of QOL between the two groups(p>0.05) before treatment. Conclusion: NCRT is safer and more effective in patients with AGC compared with NCT, and can significantly improve the QOL of patients. It can be widely used in clinical practice.
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OBJECTIVES: This study aims to introduce a novel predictive model for the post-operative facial contours of patients with mandibular defect, addressing limitations in current methodologies that fail to preserve geometric features and lack interpretability. METHODS: Utilizing surface mesh theory and deep learning, our model diverges from traditional point cloud approaches by employing surface triangular mesh grids. We extract latent variables using a Mesh Convolutional Restricted Boltzmann Machines (MCRBM) model to generate a three-dimensional deformation field, aiming to enhance geometric information preservation and interpretability. RESULTS: Experimental evaluations of our model demonstrate a prediction accuracy of 91.2 %, which represents a significant improvement over traditional machine learning-based methods. CONCLUSIONS: The proposed model offers a promising new tool for pre-operative planning in oral and maxillofacial surgery. It significantly enhances the accuracy of post-operative facial contour predictions for mandibular defect reconstructions, providing substantial advancements over previous approaches.
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Introduction: Wet contamination was a common problem of peritoneal dialysis (PD) system. We developed a management algorithm for wet contamination of PD system (wet contamination) on the basis of the related research literature and clinical practice experience. The purpose of this study was to observe clinical effect of the management algorithm on the prevention of peritonitis. Methods: Patients treated wet contamination in a single PD center between October 2017 and September 2022 were included. A management algorithm was established to treat wet contamination. It comprised identification of the contamination type, addressing contaminated or aging catheters, prophylactic antibiotics, and retraining. Demographic data and clinical data about wet contamination were collected and compared. Results: One hundred and forty-one cases of wet contamination were included in this study. The mean age was 51.7 ± 14.1 years, and 49.6% were female. The proportion of diabetic nephropathy was 9.9%. The median PD duration was 27.0 (1.7-79.7) months. Eighteen episodes (12.8%) of wet contamination-associated peritonitis developed after wet contamination. The main pathogenic bacteria of peritonitis were Gram-positive bacteria (33.3%) and Gram-negative bacteria (27.8%). The incidence of wet contamination-associated peritonitis in the compliance with the management algorithm group was significantly lower than that in the non-compliance with the management algorithm group (0.9 vs. 48.6%; p < 0.001). Non-compliance with management algorithm (OR = 185.861, p < 0.001) together with advance age (OR = 1.116, p < 0.001) and longer distance from home to hospital (OR = 1.007, p < 0.001) were independent risk factors for wet contamination-associated peritonitis. Conclusion: The management algorithm for wet contamination of PD system could reduce the risk of peritonitis.
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BACKGROUND: α-Crystallin B (CRYAB) is a chaperone member of the HSPs family that protects proteins with which it interacts from degradation. This study aims to investigate the effect of CRYAB on the progression of colorectal cancer (CRC) and its underlying mechanism. METHODS: CRYAB expression was evaluated in CRC tissues. Cell growth was tested by CCK-8 kit. Lipid reactive oxygen species (ROS) assays, lipid peroxidation assays, glutathione assays were used to assess the degree of cellular lipid peroxidation of CRC cells. The potential signal pathways of CRYAB were analyzed and verified by Western blot (WB) and immunoprecipitation (Co-IP). RESULTS: CRYAB expression was elevated in CRC tissues and exhibited sensitivity and specificity in predicting CRC. Functionally, knockdown of CRYAB induced ferroptosis in CRC cells. Mechanistically, CRYAB binding prevented from ß-catenin interacting with TRIM55, leading to an increase in ß-catenin protein stability, which desensitized CRC cells to ferroptosis and ultimately accelerated cancer progression. CONCLUSIONS: Targeting CRYAB might be a promising strategy to enhance ferroptosis and improve the efficacy of CRC therapy.
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BACKGROUND: Cardiovascular magnetic resonance (CMR) has demonstrated excellent performance in the diagnosis of cardiac amyloidosis (CA). However, misdiagnosis occasionally occurs because the morphological and functional features of CA are non-specific. This study was performed to determine the value of non-contrast CMR T1ρ in the diagnosis of CA. METHODS: This prospective study included 45 patients with CA, 30 patients with hypertrophic cardiomyopathy (HCM), and 10 healthy controls (HCs). All participants underwent cine (whole heart), T1ρ mapping, pre- and post-contrast T1 mapping imaging (three slices), and late gadolinium enhancement using a 3T whole-body MRI system. All participants underwent T1ρ at two spin-locking frequencies: 0Hz and 298Hz. ECV maps were obtained using pre- and post-contrast T1 maps. The myocardial T1ρ dispersion map, termed myocardial dispersion index (MDI), was also calculated. All parameters were measured in the left ventricular myocardial wall. Participants in the HC group were scanned twice on different days to assess the reproducibility of T1ρ measurements. RESULTS: Excellent reproducibility was observed upon evaluation of the coefficient of variation between two scans (T1ρ [298Hz]: 3.1%; T1ρ [0Hz], 2.5%). The ECV (HC: 27.4 ± 2.8% vs. HCM: 32.6 ± 5.8% vs. CA: 46 ± 8.9%; p < 0.0001), T1ρ [0Hz] (HC: 35.8 ± 1.7 ms vs. HCM: 40.0 ± 4.5 ms vs. CA: 51.4 ± 4.4 ms; p < 0.0001) and T1ρ [298Hz] (HC: 41.9 ± 1.6 ms vs. HCM: 48.8 ± 6.2 ms vs. CA: 54.4 ± 5.2 ms; p < 0.0001) progressively increased from the HC group to the HCM group, and then the CA group. The MDI progressively decreased from the HCM group to the HC group, and then the CA group (HCM: 8.8 ± 2.8 ms vs. HC: 6.1 ± 0.9 ms vs. CA: 3.4 ± 2.1 ms; p < 0.0001). For differential diagnosis, the combination of MDI and T1ρ [298Hz] showed the greatest sensitivity (98.3%) and specificity (95.5%) between CA and HCM, compared with the native T1 and ECV. CONCLUSIONS: The T1ρ and MDI approaches can be used as non-contrast CMR imaging biomarkers to improve the differential diagnosis of patients with CA.
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China, as the world's largest producer, trader, and consumer of aquatic foods, lacks comprehensive research on consumption patterns and willingness to pay for sustainable aquatic food. This study addressed this gap through an online survey of 3403 participants across Chinese provinces. A majority of consumers (34.7% of the participants) consume aquatic food twice or more per week, mainly from traditional markets (26%). Most prefer fresh or live products (76%), with 42% seeing no difference between farmed and wild options. Consumption is higher among older, affluent, urban, and coastal residents. Crustaceans, especially shrimp, are frequently consumed species, with growing interest in luxury species like salmon and abalone. Taste and quality emerge as the primary factors motivating consumer choices in aquatic food purchases. Food safety is the primary concern, followed by environmental impact. Notably, 92.4% of participants would pay extra for certified products. Factors influencing a higher willingness to pay include higher income, inland residence, price sensitivity, origin consciousness, and concerns about food safety and the environment. The findings highlight that China's aquatic food industry and consumption can become more sustainable by aligning with consumer preferences for high-quality and diverse aquatic food through both production and import, while also addressing concerns related to food safety and environmental impact. This research provides valuable insights into China's rapidly transforming aquatic food market landscape, offering implications for industry innovation and the promotion of sustainable consumption patterns.
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Peripheral blood mononuclear cells (PBMC), sourced autologously, offer numerous advantages when procured: easier acquisition process, no in vitro amplification needed, decreased intervention and overall increased acceptability make PBMC an attractive candidate for cell therapy treatment. However, the exact mechanism by which PBMC treat diseases remains poorly understood. Immune imbalance is the pathological basis of many diseases, with macrophages playing a crucial role in this process. However, research on the role and mechanisms of PBMC in regulating macrophages remains scarce. This study employed an in vitro co-culture model of PBMC and RAW264.7 macrophages to explore the role and mechanisms of PBMC in regulating macrophages. The results showed that the co-culturing led to decreased expression of inflammatory cytokines and increased expression of anti-inflammatory cytokines in RAW264.7 or in the culture supernatant. Additionally, the pro-inflammatory, tissue matrix-degrading M1 macrophages decreased, while the anti-inflammatory, matrix-synthesizing, regenerative M2 macrophages increased in both RAW264.7 and monocytes within PBMC. Moreover, co-cultured macrophages exhibited a significantly decreased p-STAT1/STAT1 ratio, while the p-STAT6/STAT6 ratio significantly increased. This suggests that PBMC may inhibit M1 macrophage polarization by blocking STAT1 signaling cascades and may promote M2 macrophage polarization through the activation of STAT6 signaling cascades. Overall, this study sheds light on the role and mechanism of PBMC in regulating macrophages. Moreover, it was found that monocytes within co-cultured PBMC differentiated into M2 macrophages in the presence of macrophages. This finding provides experimental evidence for the use of PBMC in treating inflammatory diseases, especially macrophage-depleting inflammatory diseases such as osteoarthritis.
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Técnicas de Cocultivo , Leucocitos Mononucleares , Macrófagos , Factor de Transcripción STAT1 , Factor de Transcripción STAT6 , Transducción de Señal , Animales , Ratones , Citocinas/metabolismo , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Activación de Macrófagos , Macrófagos/inmunología , Macrófagos/metabolismo , Células RAW 264.7 , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT6/metabolismoRESUMEN
This study investigates the deformation and damage characteristics of the surrounding rock along the top return mining roadway of an isolated island working face at different stages and reveals its damage mechanism and evolution law. Utilizing a mine in Yangquan City, Shanxi Province, China, as the engineering background, this research employs FLAC 3D numerical simulation and on-site measurements. The findings suggest that the evolution of the plastic zone along the top roadway of the 15,106 island face is largely similar during both the excavation and mining periods. The plastic zones on either side of the roadway are expanding asymmetrically and gradually merging into the plastic zone of the coal pillar. In the destructive stage, the sub-gangs of the roadway are penetrated, indicating the progression into the plastic zone. The investigation points to extensive damage on the larger side of the roadway, the development of fissures, and the significant depth of damage as primary causes of roadway deformation. Moreover, the extent of the plastic zones on both sides of the roadway correlates positively with their relative distance. Continuous monitoring reveals an ongoing increase in roadway displacement, consistent with general observations in coal mining. The results provide valuable insights for optimizing support structures in similar mining environments.
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Cigarette smoke (CS) has been generally recognized as a chief carcinogenic factor in renal cell carcinoma (RCC). The stimulative effect of CS on renal cancer stem cells (RCSCs) has been described previously. The Sonic Hedgehog (SHH) pathway plays an essential role in self-renewal, cell growth, drug resistance, metastasis, and recurrence of cancer stem cells (CSCs). Renal cancer-related gene ΔNp63α is highly expressed in renal epithelial tissues and contributes to the RCSCs characteristics of tumors. The aim of this study was to elucidate the role of ΔNp63α and the SHH pathway on the activity of RCSCs induced by CS through a series of in vivo and in vitro studies. It was shown that in renal cancer tissues, ΔNp63α and RCSCs markers in smokers are expressed higher than that in non-smokers. RCSCs were effectively enriched by tumor sphere formation assay. Besides, CS increased the expression of RCSCs markers and the capability of sphere-forming in vitro and in vivo. Moreover, the SHH pathway was activated, and the specialized inhibitor alleviated the promotion of CS on RCSCs. ΔNp63α activated the SHH pathway and promoted CS-induced enhancement of RCSCs activity. These findings indicate that ΔNp63α positively regulates the activity of CS-induced RCSCs via the SHH pathway.
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The conceptualization and deployment of electrode materials for rechargeable sodium-ion batteries are key concerns for next-generation energy storage systems. In this contribution, the configuration stability of single-layer GeSiBi2 is systematically discussed based on first-principles calculations, and its potential as an anode material is further investigated. It is demonstrated that the phonon spectrum confirms the dynamic stability and the adsorption energy identifies a strong interaction between Na atoms and the substrate material. The electronic bands indicative of inherent metallicity contribute to the enhancement of electronic conductivity after Na adsorption. The multilayer adsorption of Na provides a theoretical capacity of 361.7 mAh/g, which is comparable to that of other representative two-dimensional anode materials. Moreover, the low diffusion barriers of 0.19 and 0.15 eV further guarantee the fast diffusion kinetics. These contributions signal that GeSiBi2 can be a compatible candidate for sodium-ion batteries anodes.
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African swine fever (ASF) is an acute and severe infectious disease caused by the African Swine Fever Virus (ASFV). ASFV exhibits significant resistance and stability in the environment, which, coupled with its double-stranded DNA and large genome, predisposes it to contaminate laboratory samples. This characteristic can lead to false-positive results in swine farm settings even days after disinfection, as detectable through polymerase chain reaction (PCR) or real-time fluorescent quantitative PCR (qPCR) assays. To meet the demand for efficient clinical methods capable of discriminating between ASFV nucleic acid and ASFV virions, this study aims to ascertain the efficacy of the nuclease "BenzoNuclease" in distinguishing ASFV nucleic acid (ASFV-DNA) from ASFV virions. BenzoNuclease is a versatile nucleic acid enzyme with the capacity to degrade nearly all forms of DNA and RNA. Initially, this research established a highly sensitive general PCR detection method for ASFV. Subsequently, a positive control was constructed using the M13 bacteriophage to substitute for active ASFV, facilitating the development of an improved qPCR method. It is important to note that common disinfectants have the potential to deactivate BenzoNuclease. However, in an environment simulating actual production applications, residual disinfectants do not interfere with the enzymatic efficacy of BenzoNuclease, thus not affecting the detection capabilities of this method. Positive clinical samples from pig farms, upon testing with the improved method, revealed that three samples were positive, indicating the presence of viral particles, while the remaining samples were negative, indicating the presence of nucleic acids. This provides an additional new option for sample testing in pig farms.
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Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , ADN Viral , Virión , Virus de la Fiebre Porcina Africana/genética , Animales , Porcinos , Fiebre Porcina Africana/virología , ADN Viral/genética , Virión/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodosRESUMEN
The high infiltration of tumor-associated macrophages (TAMs) in the immunosuppressive tumor microenvironment prominently attenuates the efficacy of immune checkpoint blockade (ICB) therapies, yet the underlying mechanisms are not fully understood. Here, we investigate the metabolic profile of TAMs and identify S-2-hydroxyglutarate (S-2HG) as a potential immunometabolite that shapes macrophages into an antitumoral phenotype. Blockage of L-2-hydroxyglutarate dehydrogenase (L2HGDH)-mediated S-2HG catabolism in macrophages promotes tumor regression. Mechanistically, based on its structural similarity to α-ketoglutarate (α-KG), S-2HG has the potential to block the enzymatic activity of 2-oxoglutarate-dependent dioxygenases (2-OGDDs), consequently reshaping chromatin accessibility. Moreover, S-2HG-treated macrophages enhance CD8+ T cell-mediated antitumor activity and sensitivity to anti-PD-1 therapy. Overall, our study uncovers the role of blockage of L2HGDH-mediated S-2HG catabolism in orchestrating macrophage antitumoral polarization and, further, provides the potential of repolarizing macrophages by S-2HG to overcome resistance to anti-PD-1 therapy.
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Glutaratos , Macrófagos , Neoplasias , Animales , Femenino , Humanos , Ratones , Oxidorreductasas de Alcohol/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Línea Celular Tumoral , Polaridad Celular/efectos de los fármacos , Glutaratos/metabolismo , Activación de Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/inmunología , Ratones Endogámicos C57BL , Neoplasias/inmunología , Neoplasias/patología , Neoplasias/metabolismo , Microambiente Tumoral , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/efectos de los fármacosRESUMEN
Rationale: It has been emergingly recognized that apoptosis generates plenty of heterogeneous apoptotic vesicles (apoVs), which play a pivotal role in the maintenance of organ and tissue homeostasis. However, it is unknown whether apoVs influence postnatal ovarian folliculogenesis. Methods: Apoptotic pathway deficient mice including Fas mutant (Fasmut ) and Fas ligand mutant (FasLmut ) mice were used with apoV replenishment to evaluate the biological function of apoVs during ovarian folliculogenesis. Ovarian function was characterized by morphological analysis, biochemical examination and cellular assays. Mechanistical studies were assessed by combinations of transcriptomic and proteomic analysis as well as molecular assays. CYP17A1-Cre; Axin1fl /fl mice was established to verify the role of WNT signaling during ovarian folliculogenesis. Polycystic ovarian syndrome (PCOS) mice and 15-month-old mice were used with apoV replenishment to further validate the therapeutic effects of apoVs based on WNT signaling regulation. Results: We show that systemic administration of mesenchymal stem cell (MSC)-derived apoptotic vesicles (MSC-apoVs) can ameliorate impaired ovarian folliculogenesis, PCOS phenotype, and reduced birth rate in Fasmut and FasLmut mice. Mechanistically, transcriptome analysis results revealed that MSC-apoVs downregulated a number of aberrant gene expression in Fasmut mice, which were enriched by kyoto encyclopedia of genes and genomes (KEGG) pathway analysis in WNT signaling and sex hormone biosynthesis. Furthermore, we found that apoptotic deficiency resulted in aberrant WNT/ß-catenin activation in theca and mural granulosa cells, leading to responsive action of dickkopf1 (DKK1) in the cumulus cell and oocyte zone, which downregulated WNT/ß-catenin expression in oocytes and, therefore, impaired ovarian folliculogenesis via NPPC/cGMP/PDE3A/cAMP cascade. When WNT/ß-catenin was specially activated in theca cells of CYP17A1-Cre; Axin1fl /fl mice, the same ovarian impairment phenotypes observed in apoptosis-deficient mice were established, confirming that aberrant activation of WNT/ß-catenin in theca cells caused the impairment of ovarian folliculogenesis. We firstly revealed that apoVs delivered WNT membrane receptor inhibitor protein RNF43 to ovarian theca cells to balance follicle homeostasis through vesicle-cell membrane integration. Systemically infused RNF43-apoVs down-regulated aberrantly activated WNT/ß-catenin signaling in theca cells, contributing to ovarian functional maintenance. Since aging mice have down-regulated expression of WNT/ß-catenin in oocytes, we used MSC-apoVs to treat 15-month-old mice and found that MSC-apoVs effectively ameliorated the ovarian function and fertility capacity of these aging mice through rescuing WNT/ß-catenin expression in oocytes. Conclusion: Our studies reveal a previously unknown association between apoVs and ovarian folliculogenesis and suggest an apoV-based therapeutic approach to improve oocyte function and birth rates in PCOS and aging.
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Apoptosis , Células Madre Mesenquimatosas , Folículo Ovárico , Ovario , Síndrome del Ovario Poliquístico , Vía de Señalización Wnt , Animales , Femenino , Síndrome del Ovario Poliquístico/metabolismo , Ratones , Células Madre Mesenquimatosas/metabolismo , Folículo Ovárico/metabolismo , Ovario/metabolismo , Modelos Animales de Enfermedad , Envejecimiento/fisiología , Proteína Ligando Fas/metabolismo , Proteína Ligando Fas/genéticaRESUMEN
OBJECTIVE: To evaluate the outcome of Augmented reality technology in the recognizing of oral and maxillofacial anatomy. METHODS: This study was conducted on the undergraduate students in Peking University School of Stomatology who were learning oral and maxillofacial anatomy. The image data were selected according to the experiment content, and the important blood vessels and bone tissue structures, such as upper and lower jaws, neck arteries and veins were reconstructed in 3D(3-dimensional) by digital software to generate experiment models, and the reconstructed models were encrypted and stored in the cloud. The QR (quick response) code corresponding to the 3D model was scanned by a networked mobile device to obtain augmented reality images to assist experimenters in teaching and subjects in recognizing. Augmented reality technology was applied in both the theoretical explanation and cadaveric dissection respectively. Subjects' feedback was collected in the form of a post-class questionnaire to evaluate the effectiveness of augmented reality technology-assisted recognizing. RESULTS: In the study, 83 undergraduate students were included as subjects in this study. Augmented reality technology could be successfully applied in the recognizing of oral and maxillofacial anatomy. All the subjects could scan the QR code through a connected mobile device to get the 3D anatomy model from the cloud, and zoom in/out/rotate the model on the mobile. Augmented reality technology could provide personalized 3D model, based on learners' needs and abilities. The results of likert scale showed that augmented reality technology was highly recognized by the students (9.19 points), and got high scores in terms of forming a three-dimensional sense and stimulating the enthusiasm for learning (9.01 and 8.85 points respectively). CONCLUSION: Augmented reality technology can realize the three-dimensional visualization of important structures of oral and maxillofacial anatomy and stimulate students' enthusiasm for learning. Besides, it can assist students in building three-dimensional space imagination of the anatomy of oral and maxillofacial area. The application of augmented reality technology achieves favorable effect in the recognizing of oral and maxillofacial anatomy.
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Realidad Aumentada , Imagenología Tridimensional , Humanos , Imagenología Tridimensional/métodos , Anatomía/educación , Boca/anatomía & histología , Programas InformáticosRESUMEN
Speech enhancement aims to make noisy speech signals clearer. Traditional time-frequency domain methods struggle to differentiate between speech and noise, leading to a risk of speech distortion. This paper introduces an approach that combines the time domain and time-frequency domain using the W-net module to suppress noise at the front end. The module is an improved version of Wave-U-Net, called TTF-W-Net. We conducted experiments using the TIMIT speech and NOISEX-92 noise datasets to evaluate the enhancement performance achieved by integrating preprocessing networks, specifically Wave-U-Net and our TTF-W-Net, into the baseline methods: Phase, FullSubNet+, and DB-AIAT. Experimental results show that TTF-W-Net outperforms the baseline Wave-U-Net by 15.7% on the PESQ metric and the effect of the network by using our preprocessing method is improved. Consequently, the TTF-W-Net preprocessing Net offers effective speech enhancement.
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The cachexia index is a novel indicator of cachexia, but its prognostic implications for survival outcomes have not been systematically assessed in patients with gastrointestinal cancer. This systematic review and meta-analysis aimed to examine the association between the cachexia index and survival outcomes in gastrointestinal cancer patients. Two independent reviewers searched PubMed, Embase, and Web of Science to identify studies that evaluated the prognostic significance of the cachexia index in patients with gastrointestinal cancer. The prognostic value of the cachexia index was determined by combining the adjusted hazard ratios (HR) and 95% confidence intervals (CI). Thirteen studies were identified, including a total of 4207 patients. Meta-analysis indicated that a lower cachexia index was associated with shorter overall survival (HR 2.18; 95% CI 1.78-2.66) and disease-free survival (HR 1.72; 95% CI 1.50-1.97) in gastrointestinal cancer patients. Further stratified analysis confirmed the significant association between a lower cachexia index and shorter overall survival in different study designs, regions, patients' age, sample sizes, gastrointestinal cancer subtypes, tumor stages, and follow-up duration subgroups. The cachexia index could be utilized as a predictor of overall survival and disease-free survival in patients with gastrointestinal cancer. However, future prospective studies are required to confirm these findings.
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[This corrects the article DOI: 10.3389/fphar.2023.900205.].
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In this study, processing tomato (Solanum lycopersicum L.) 'Ligeer 87-5' was hydroponically cultivated under 100 mM NaCl to simulate salt stress. To investigate the impacts on ion homeostasis, osmotic regulation, and redox status in tomato seedlings, different endogenous levels of ascorbic acid (AsA) were established through the foliar application of 0.5 mM AsA (NA treatment), 0.25 mM lycorine (LYC, an inhibitor of AsA synthesis; NL treatment), and a combination of LYC and AsA (NLA treatment). The results demonstrated that exogenous AsA significantly increased the activities and gene expressions of key enzymes (L-galactono-1,4-lactone dehydrogenase (GalLDH) and L-galactose dehydrogenase (GalDH)) involved in AsA synthesis in tomato seedling leaves under NaCl stress and NL treatment, thereby increasing cellular AsA content to maintain its redox status in a reduced state. Additionally, exogenous AsA regulated multiple ion transporters via the SOS pathway and increased the selective absorption of K+, Ca2+, and Mg2+ in the aerial parts, reconstructing ion homeostasis in cells, thereby alleviating ion imbalance caused by salt stress. Exogenous AsA also increased proline dehydrogenase (ProDH) activity and gene expression, while inhibiting the activity and transcription levels of Δ1-pyrroline-5-carboxylate synthetase (P5CS) and ornithine-δ-aminotransferase (OAT), thereby reducing excessive proline content in the leaves and alleviating osmotic stress. LYC exacerbated ion imbalance and osmotic stress caused by salt stress, which could be significantly reversed by AsA application. Therefore, exogenous AsA application increased endogenous AsA levels, reestablished ion homeostasis, maintained osmotic balance, effectively alleviated the inhibitory effect of salt stress on tomato seedling growth, and enhanced their salt tolerance.
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Raman spectroscopy has become an important single-cell analysis tool for monitoring biochemical changes at the cellular level. However, Raman spectral data, typically presented as continuous data with high-dimensional characteristics, is distinct from discrete sequences, which limits the application of deep learning-based algorithms in data analysis due to the lack of discretization. Herein, a model called fragment-fusion transformer is proposed, which integrates the discrete fragmentation of continuous spectra based on their intrinsic characteristics with the extraction of intrafragment features and the fusion of interfragment features. The model integrates the intrinsic feature-based fragmentation of spectra with transformer, constructing the fragment transformer block for feature extraction within fragments. Interfragment information is combined through the pyramid design structure to improve the model's receptive field and fully exploit the spectral properties. During the pyramidal fusion process, the information gain of the final extracted features in the spectrum has been enhanced by a factor of 9.24 compared to the feature extraction stage within the fragment, and the information entropy has been enhanced by a factor of 13. The fragment-fusion transformer achieved a spectral recognition accuracy of 94.5%, which is 4% higher compared to the method without fragmentation and fusion processes on the test set of cell Raman spectroscopy identification experiments. In comparison to common spectral classification models such as KNN, SVM, logistic regression, and CNN, fragment-fusion transformer has achieved 4.4% higher accuracy than the best-performing CNN model. Fragment-fusion transformer method has the potential to serve as a general framework for discretization in the field of continuous spectral data analysis and as a research tool for analyzing the intrinsic information within spectra.
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Aprendizaje Profundo , Análisis de la Célula Individual , Espectrometría Raman , Espectrometría Raman/métodos , Análisis de la Célula Individual/métodos , Humanos , AlgoritmosRESUMEN
African swine fever virus (ASFV) causes severe disease in domestic pigs and wild boars, seriously threatening the development of the global pig industry. Type I interferon (IFN-I) is an important component of innate immunity, inducing the transcription and expression of antiviral cytokines by activating Janus-activated kinase-signal transducer and activator of transcription (STAT). However, the underlying molecular mechanisms by which ASFV antagonizes IFN-I signaling have not been fully elucidated. Therefore, using coimmunoprecipitation, confocal microscopy, and dual luciferase reporter assay methods, we investigated these mechanisms and identified a novel ASFV immunosuppressive protein, pB475L, which interacts with the C-terminal domain of STAT2. Consequently, pB475L inhibited IFN-I signaling by inhibiting STAT1 and STAT2 heterodimerization and nuclear translocation. Furthermore, we constructed an ASFV-B475L7PM mutant strain by homologous recombination, finding that ASFV-B475L7PM attenuated the inhibitory effects on IFN-I signaling compared to ASFV-WT. In summary, this study reveals a new mechanism by which ASFV impairs host innate immunity.