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SCOPE: Ferroptosis has been demonstrated to play an important role in various tissue injuries and diseases. Flaxseed oil (FO) has been proven to have benefits for intestinal health. This study aims to explore whether FO relieved lipopolysaccharide (LPS)-induced intestinal injury through modulating ferroptosis signaling pathway. METHODS AND RESULTS: A total of 120 weaned piglets are fed diets with 3% soybean oil (SO) or 3% FO for 4 weeks. At the end of the trial, 24 piglets selected from two dietary treatment groups are used in a 2 × 2 factorial design with oil treatment (3% SO versus 3% FO) and LPS challenge (saline versus LPS). At 4 h postinjection with LPS, 24 piglets are slaughtered and intestinal samples are collected. FO improves growth performance of pigs. After LPS treatment, FO mitigates intestinal morphological damage and functional damage. Notably, FO reverses the typical ultra-morphology and biochemical indexes of ferroptosis involving glutathione, malondialdehyde, and 4-hydroxynonenal contents. Mechanistically, FO ameliorates the changes on mRNA or protein abundance of key ferroptosis signals including transferrin receptor protein 1 (TFR1), recombinant iron responsive element binding protein 2 (IREB2), FTL, HSPB1, ferritin heavy chain 1 (FTH1), ferroportin 1 (FPN1), SLC7A11, solute carrier family 3 member 2 (SLC3A2), glutathione peroxidase 4 (GPX4), and arachidonate-15-lipoxygenase (ALOX15). CONCLUSIONS: FO improves growth performance and mitigates intestinal structural and functional damage, which is involved in regulating ferroptosis signaling pathway.
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BACKGROUND: Although cone beam computed tomography (CBCT) has lower resolution compared to planning CTs (pCT), its lower dose, higher high-contrast resolution, and shorter scanning time support its widespread use in clinical applications, especially in ensuring accurate patient positioning during the image-guided radiation therapy (IGRT) process. PURPOSE: While CBCT is critical to IGRT, CBCT image quality can be compromised by severe stripe and scattering artifacts. Tumor movement secondary to respiratory motion also decreases CBCT resolution. In order to improve the image quality of CBCT, we propose a Lung Diffusion Model (L-DM) framework. METHODS: Our proposed algorithm is based on a conditional diffusion model trained on pCT and deformed CBCT (dCBCT) image pairs to synthesize lung CT images from dCBCT images and benefit CBCT-based radiotherapy. dCBCT images were used as the constraint for the L-DM. The image quality and Hounsfield unit (HU) values of the synthetic CTs (sCT) images generated by the proposed L-DM were compared to three selected mainstream generation models. RESULTS: We verified our model in both an institutional lung cancer dataset and a selected public dataset. Our L-DM showed significant improvement in the four metrics of mean absolute error (MAE), peak signal-to-noise ratio (PSNR), normalized cross-correlation (NCC), and structural similarity index measure (SSIM). In our institutional dataset, our proposed L-DM decreased the MAE from 101.47 to 37.87 HU and increased the PSNR from 24.97 to 29.89 dB, the NCC from 0.81 to 0.97, and the SSIM from 0.80 to 0.93. In the public dataset, our proposed L-DM decreased the MAE from 173.65 to 58.95 HU, while increasing the PSNR, NCC, and SSIM from 13.07 to 24.05 dB, 0.68 to 0.94, and 0.41 to 0.88, respectively. CONCLUSIONS: The proposed L-DM significantly improved sCT image quality compared to the pre-correction CBCT and three mainstream generative models. Our model can benefit CBCT-based IGRT and other potential clinical applications as it increases the HU accuracy and decreases the artifacts from input CBCT images.
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Objective: To investigate the effects of a PD-1 inhibitor combined with a bevacizumab monoclonal antibody on tumor immune cells in patients with first-line treatment failure in MSS/pMMR advanced colorectal cancer. Methods: Control group consisted of 50 patients treated with the FOLFIRI combined with Bevacizumab regimen. The experimental group consisted of 60 patients treated with the Sintilimab combined with Bevacizumab regimen. By comparing the expression levels of CD8+ T lymphocytes, TAMs, and CAFs before and after treatment, short-term efficacy after treatment, and adverse drug reactions between the two groups, we comprehensively evaluated the impact of Sintilimab combined with Bevacizumab on patients with MSS/pMMR advanced colorectal cancer who failed first-line treatment. Results: There was a statistically significant difference in the percentage of CD8+ T lymphocytes, TAMs, and CAFs before and after treatment between the two groups (P<0.05);Immunohistochemical scoring of CD8+ T lymphocytes, TAMs, and CAFs showed significant differences between the groups post-treatment (P<0.05). The experimental group demonstrated statistically significant differences in immunohistochemical scoring of CD8+ T lymphocytes, TAMs, and CAFs before and after treatment (P<0.05). There was a statistically significant difference in the therapeutic effect between the two groups of tumors (P<0.05). The experimental group had greater PFS, mPFS, ORR, and DCR than did the control group. There was no statistically significant difference in the occurrence rate of drug-related adverse reactions after treatment between the two groups (P>0.05). The results of the Cox proportional hazards model analysis indicate that age, gender, and group are independent risk factors affecting MSS/pMMR advanced colorectal cancer patients treated with second-line therapy in this study. Patients aged ≤60 years, male patients, and those in the experimental group showed better treatment responses in this study. Conclusion: By administering immune checkpoint inhibitors in combination with bevacizumab to patients with advanced colorectal cancer with MSS/pMMR disease for whom first-line treatment failed, not only did the patients' prognosis improve, but the adverse drug reactions were also safe and controllable.
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2'-5'-Adenosine linked nucleic acids are crucial components in living cells that play significant roles, including participating in antiviral defense mechanisms by facilitating the breakdown of viral genetic material. In this report, we present a chemical derivatization method employing 5-fluoro-2-pyridinoyl-imidazole as the acylation agent, a strategy that can be effectively combined with advanced analytical tools, including Nuclear Magnetic Resonance spectroscopy and Liquid Chromatography-Mass Spectrometry, to enhance the characterization and detection capabilities. This marks the first instance of a simple method designed to detect 2'-5'-adenosine linked nucleic acids. The new method is characterized by its time-saving nature, simplicity, and relative accuracy compared to previous methods.
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Adenosina , Acilação , Adenosina/química , Adenosina/análogos & derivados , Adenosina/análise , Ácidos Nucleicos/química , Ácidos Nucleicos/análise , Imidazóis/química , Estrutura Molecular , Espectroscopia de Ressonância Magnética , Espectrometria de MassasRESUMO
BACKGROUND: The study of changes in the microbiome in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) holds significant potential for developing noninvasive diagnostic tools as well as innovative interventions to alter the progression of diseases. This systematic review and meta-analysis aimed to analyze in detail the taxonomic and functional characteristics of the gut microbiome in patients with CP and PDAC. METHODS: Two researchers conducted a systematic search across public databases to gather all published research up to June 2023. Diversity and gut microbiota composition are the main outcomes we focus on. RESULTS: This meta-analysis included 14 studies, involving a total of 1511 individuals in the PDAC (n=285), CP (n=342), and control (n=649) groups. Our results show a significant difference in the composition of gut microbiota between PDAC/CP patients compared to healthy controls (HC), as evidenced by a slight decrease in α-diversity, including Shannon (SMD=-0.33; P=0.002 and SMD=-0.59; P<0.001, respectively) and a statistically significant ß-diversity (P<0.05). The pooled results showed that at the phylum level, the proportion of Firmicutes was lower in PDAC and CP patients than in HC patients. At the genus level, more than two studies demonstrated that 4 genera were significantly increased in PDAC patients compared to HC (e.g., Escherichia-Shigella and Veillonella). CP patients had an increase in 4 genera (e.g., Escherichia-Shigella and Klebsiella) and a decrease in 8 genera (e.g., Coprococcus and Bifidobacterium) compared to HC. Functional/metabolomics results from various studies also showed differences between PDAC/CP patients and HC. In addition, this study found no significant differences in gut microbiota between PDAC and CP patients. CONCLUSIONS: Current evidence suggests changes in gut microbiota is associated with PDAC/CP, commonly reflected by a reduction in beneficial species and an increase in the pathogenic species. Further studies are needed to confirm these findings and explore therapeutic possibilities.
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The rising accumulation of poly(ethylene terephthalate) (PET) waste presents an urgent ecological challenge, necessitating an efficient and economical treatment technology. Here, we developed chemical-biological module clusters that perform chemical pretreatment, enzymatic degradation, and microbial assimilation for the large-scale treatment of PET waste. This module cluster included (i) a chemical pretreatment that involves incorporating polycaprolactone (PCL) at a weight ratio of 2% (PET:PCL = 98:2) into PET via mechanical blending, which effectively reduces the crystallinity and enhances degradation; (ii) enzymatic degradation using Thermobifida fusca cutinase variant (4Mz), that achieves complete degradation of pretreated PET at 300 g/L PET, with an enzymatic loading of 1 mg protein per gram of PET; and (iii) microbial assimilation, where Rhodococcus jostii RHA1 metabolizes the degradation products, assimilating each monomer at a rate above 90%. A comparative life cycle assessment demonstrated that the carbon emissions from our module clusters (0.25 kg CO2-eq/kg PET) are lower than those from other established approaches. This study pioneers a closed-loop system that seamlessly incorporates pretreatment, degradation, and assimilation processes, thus mitigating the environmental impacts of PET waste and propelling the development of a circular PET economy.
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Biodegradação Ambiental , Poliésteres , Polietilenotereftalatos , Polietilenotereftalatos/química , Polietilenotereftalatos/metabolismo , Poliésteres/metabolismo , Poliésteres/química , Hidrolases de Éster CarboxílicoRESUMO
Chemical modifications in RNAs play crucial roles in diversifying their structures and regulating numerous biochemical processes. Since the 1990s, several hydrophobic prenyl-modifications have been discovered in various RNAs. Prenyl groups serve as precursors for terpenes and many other biological molecules. The processes of prenylation in different macromolecules have been extensively studied. We introduce here a novel chemical biology toolkit that not only labels i6A, a prenyl-modified RNA residue, by leveraging the unique reactivity of the prenyl group, but also provides a general strategy to incorporate fluorescence functionalities into RNAs for molecular tracking purposes. Our findings revealed that iodine-mediated cyclization reactions of the prenyl group occur rapidly, transforming i6A from a hydrogen-bond acceptor to a donor. Based on this reactivity, we developed an Iodine-Mediated Cyclization and Reverse Transcription (IMCRT) tRNA-seq method, which can profile all nine endogenous tRNAs containing i6A residues in Saccharomyces cerevisiae with single-base resolution. Furthermore, under stress conditions, we observed a decline in i6A levels in budding yeast, accompanied by significant decrease of mutation rate at A37 position. Thus, the IMCRT tRNA-seq method not only permits semi-quantification of i6A levels in tRNAs but also holds potential for transcriptome-wide detection and analysis of various RNA species containing i6A modifications.
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Isopenteniladenosina , Processamento Pós-Transcricional do RNA , RNA de Transferência , Iodo , Neopreno , RNA de Transferência/metabolismo , Saccharomyces cerevisiae , Análise de Sequência de RNARESUMO
Stevens-Johnson syndrome or toxic epidermal necrolysis (TEN) is a severe skin and mucosal reaction that develops rapidly and has a high mortality rate. Its early identification and proper treatment are crucial to lowering the risk of death. Severe TEN can also lead to acute respiratory failure. This study probed the effect of early treatment on chronic airway damage in children with TEN complicated by respiratory failure. Three children diagnosed with TEN complicated by respiratory failure received interventions including high-dose glucocorticoids, gamma-globulin pulse therapy, and plasma exchange. One patient experienced recurrent lung infections, developed secondary chronic obstructive pulmonary disease, and eventually succumbed to respiratory failure despite skin improvement. The other two patients showed improvement after receiving combination treatment with a tumor necrosis factor-α (TNF-α) inhibitor. However, they also had concurrent chronic airway disease during the follow-up period. The exact mechanism underlying TEN remains uncertain. Children with TEN complicated by respiratory failure continue to experience chronic airway damage even after standard treatment. In future, multi-center clinical studies are warranted to investigate the impact of TNF-α inhibitors in children with TEN. Assessing the effectiveness and safety of targeted medications for TEN will provide more evidence regarding the prognosis of this disease.
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BACKGROUND: Esophagectomy is the main treatment for esophageal squamous cell carcinoma (ESCC), and patients with histopathologically negative margins still have a relatively higher recurrence rate. Contrast-enhanced CT (CECT) radiomics might noninvasively obtain potential information about the internal heterogeneity of ESCC and its adjacent tissues. This study aimed to develop CECT radiomics models to preoperatively identify the differences between tumor and proximal tumor-adjacent and tumor-distant tissues in ESCC to potentially reduce tumor recurrence. METHODS: A total of 529 consecutive patients with ESCC from Centers A (n = 447) and B (n = 82) undergoing preoperative CECT were retrospectively enrolled in this study. Radiomics features of the tumor, proximal tumor-adjacent (PTA) and proximal tumor-distant (PTD) tissues were individually extracted by delineating the corresponding region of interest (ROI) on CECT and applying the 3D-Slicer radiomics module. Patients with pairwise tissues (ESCC vs. PTA, ESCC vs. PTD, and PTA vs. PTD) from Center A were randomly assigned to the training cohort (TC, n = 313) and internal validation cohort (IVC, n = 134). Univariate analysis and the least absolute shrinkage and selection operator were used to select the core radiomics features, and logistic regression was performed to develop radiomics models to differentiate individual pairwise tissues in TC, validated in IVC and the external validation cohort (EVC) from Center B. Diagnostic performance was assessed using area under the receiver operating characteristics curve (AUC) and accuracy. RESULTS: With the chosen 20, 19 and 5 core radiomics features in TC, 3 individual radiomics models were developed, which exhibited excellent ability to differentiate the tumor from PTA tissue (AUC: 0.965; accuracy: 0.965), the tumor from PTD tissue (AUC: 0.991; accuracy: 0.958), and PTA from PTD tissue (AUC: 0.870; accuracy: 0.848), respectively. In IVC and EVC, the models also showed good performance in differentiating the tumor from PTA tissue (AUCs: 0.956 and 0.962; accuracy: 0.956 and 0.937), the tumor from PTD tissue (AUCs: 0.990 and 0.974; accuracy: 0.952 and 0.970), and PTA from PTD tissue (AUCs: 0.806 and 0.786; accuracy: 0.760 and 0.786), respectively. CONCLUSION: CECT radiomics models could differentiate the tumor from PTA tissue, the tumor from PTD tissue, and PTA from PTD tissue in ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/cirurgia , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/cirurgia , Radiômica , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Microplastics (MPs) are emerging pollutants that have been globally found in the environment, and have become a focus of intensive management for the Shanghai government in China. Although there are several studies reporting the abundance of microplastics (MPs) in different matrices in Shanghai city, the general data are still limited. This work comprehensively reviews microplastic (MP) pollution in the water, sediment, atmosphere, and soil of Shanghai during 2013-2022. A summary of characteristics such as the abundance, shape, and polymer composition of MPs is presented. Additionally, the pollution trends, traceability, and ecological risks of MPs are analyzed and evaluated. Based on the analytical results, we find that the inland water in Shanghai city is the most contaminated with the highest abundance of MPs at 14.76 × 103 particles/m3 on average, while the abundances of MPs in the external water, inland sediment, external sediment, indoor atmosphere, outdoor atmosphere, inland soil, and external soil are 2.78 × 103 particles/m3, 0.80 × 103 particles/kg, 1.37 × 103 particles/kg, 0.03 × 103 particles/m3, 0.08 × 103 particles/m3, 0.27 × 103 particles/kg, and 0.18 × 103 particles/kg, respectively. Polyethylene and polypropylene are the top two detected polymer compositions of MPs. Results of ecological risk assessment using risk index and pollution load index models indicate that the risks of MPs in the water and sediment of the Yangtze Estuary are high. It is noteworthy that the abundances of MPs at the junction site of Suzhou Creek and the Huangpu River as well as in the Yangtze Estuary exhibited an increasing trend between 2017 and 2019. This work contributes to a comprehensive overview of MPs in the environment of Shanghai city during 2013-2022 and provides important data for local governments to develop urgent strategies for the management of MP pollution. However, more investigations are increasingly needed for better understand the production, migration, ecological risk, and management of MPs in the environment of Shanghai city.
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BACKGROUND: Cherry tomatoes are nutritious and favored by consumers. Processing them into dried cherry tomatoes can prolong their storage life and improve their flavor. The pretreatment of tomato pericarp is crucial for the subsequent processing. However, the traditional physical and chemical treatments of tomato pericarp generally cause nutrient loss and environmental pollution. RESULTS: In this study, a novel enzymatic method for cherry tomatoes was performed using mixed enzymes containing cutinase, cellulase and pectinase. Results showed that the pericarp permeability of cherry tomatoes was effectively improved due to enzymatic treatment. Changes in the microscopic structure and composition of the cuticle were revealed. After treatment with different concentrations of enzymes, cherry tomatoes exhibited higher pericarp permeability and sensory quality to varying degrees. The lycopene content and total polyphenol content significantly increased 2.4- and 1.45-fold, respectively. In addition, the satisfactory effect of the six-time reuse of enzymes on cherry tomatoes could still reach the same level as the initial effect, which effectively reduced the cost of production. CONCLUSIONS: This study revealed for the first time that a mixed enzymatic treatment consisting of cutinase, pectinase and cellulase could effectively degrade the cuticle, enhance the pericarp permeability and improve the quality of cherry tomatoes, with the advantages of being mildly controllable and environmentally friendly, providing a new strategy for the processing of dried cherry tomatoes. © 2023 Society of Chemical Industry.
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Celulases , Solanum lycopersicum , Poligalacturonase , Licopeno , PermeabilidadeRESUMO
Nanozymes have shown promise for antibacterial applications, but their effectiveness is often hindered by low catalytic performances in physiological conditions and uncontrolled production of hydroxyl radicals (·OH). To address these limitations, a comprehensive approach is presented through the development of an adenosine triphosphate (ATP)-activated cascade reactor (GGPcs). The GGPcs reactor synergistically combines the distinct properties of zeolitic imidazolate framework-8 (ZIF-8) and chitosan-integrated hydrogel microsphere. The ZIF-8 allows for the encapsulation of G-quadruplex/hemin DNAzyme to achieve ATP-responsive ·OH generation at neutral pH, while the hydrogel microsphere creates a confinement environment that facilitates glucose oxidation and provides a sufficient supply of H2O2. Importantly, the integrated chitosan in the hydrogel microsphere shields ZIF-8 from undesired disruption caused by gluconic acid, ensuring the responsive specificity of ZIF-8 toward ATP. By activating GGPcs with ATP secreted by bacteria, its effectiveness as an antibacterial agent is demonstrated for the on-demand treatment of bacterial infection with minimal side effects. This comprehensive approach has the potential to facilitate the design of advanced nanozyme systems and broaden their biological applications.
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Trifosfato de Adenosina , Antibacterianos , Radical Hidroxila , Radical Hidroxila/metabolismo , Trifosfato de Adenosina/metabolismo , Antibacterianos/farmacologia , Antibacterianos/química , Quitosana/química , Quitosana/farmacologia , Microesferas , Peróxido de Hidrogênio/química , Zeolitas/química , Zeolitas/farmacologiaRESUMO
The total mesorectal excision (TME) approach has been established as the gold standard for the surgical treatment of middle and lower rectal cancer. This approach is widely accepted to minimize the risk of local recurrence and increase the long-term survival rate of patients undergoing surgery. However, standardized TME causes urogenital dysfunction in more than half of patients, thus lowering the quality of life of patients. Of note, pelvic autonomic nerve damage during TME is the most pivotal cause of postoperative urogenital dysfunction. The anatomy of the Denonvilliers' fascia (DVF) and its application in surgery have been investigated both nationally and internationally. Nevertheless, controversy exists regarding the basic to clinical anatomy of DVF and its application in surgery. Currently, it is a hotspot of concern and research to improve the postoperative quality of life of patients with rectal cancer through the protection of their urinary and reproductive functions after radical resection. Herein, this study systematically describes the anatomy of DVF and its application in surgery, thus providing a reference for the selection of surgical treatment modalities and the enhancement of postoperative quality of life in patients with middle and low rectal cancer.
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We propose the introduction of the azido and azo-functionalities into prenylated derivatives under mild conditions in a selective and efficient way. Upon protocol establishment and substrate scope determination, we apply this method to prenylated protein (citronellol-BSA) labeling, chemical pulldown, and enrichment. Eventually, we achieve the degradation of RAS on MCF-7 and HeLa cell lines by employing the well-designed probe von Hippel-Lindau derivatives C4 through the sequential azidation/azolation and click-reaction (SACR) pathway targeting the prenyl functionality attached to the Caax motif of the tested RAS protein. This method displays great potential in regulation of prenylated molecules.
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Proteínas ras , Células HeLaRESUMO
Fluorinated compounds are a class of organic substances resistant to degradation. Although zero-valent iron (Fe0) has a promising reducing capability, it still fails to degrade fluorine-containing antibiotics (i.e., florfenicol) efficiently. In this study, we applied a simple one-pot pyrolytic approach to synthesize nitrogen-doped biochar supported Fe0 and zero-valent copper (Cu0) composite (Fe/Cu@NBC) and investigated its performance on florfenicol removal. The results clearly showed that approximately 91.4% of florfenicol in the deionized water was removed by Fe/Cu@NBC within 8 h. As the reaction time was extended to 15 d, the total degradation rate of florfenicol reached 96.6%, in which the defluorination and dechlorination rates were 73.2% and 82.1%, respectively. Both experimental results and density functional theory calculation suggested that âOH and ·O2- triggered ß-fluorine elimination, resulting in defluorination prior to dechlorination. This new finding was distinct from previous viewpoints that defluorination was more difficult to occur than dechlorination. Fe/Cu@NBC also had a favorable performance for removal of florfenicol in surface water. This study provides a new insight into the degradation mechanism and pathway of florfenicol removal in the Fe/Cu@NBC system, which can be a promising alternative for remediation of fluorinated organic compounds in the environment.
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Antibacterianos , Poluentes Químicos da Água , Ferro , Cobre , Nitrogênio , Flúor , Água , Poluentes Químicos da Água/análiseRESUMO
Protein degradation is emerging as a powerful strategy to modulate protein functions and alter cellular signaling pathways. Proteolysis-targeting chimeras (PROTACs) have been used to degrade a range of "undruggable" proteins in cells. Here, we present a type of chemically catalyzed PROTAC to induce rat sarcoma (RAS) degradation based on the chemistry of post-translational prenyl modification. Trimethylsilyl azide and Selectfluor were used to chemically tag the prenyl modification on Caax motif of RAS protein, and a sequential click reaction was applied using the propargyl pomalidomide probe to degrade the prenylated RAS in several cells. Thus, this approach was successfully applied to degrade RAS in multiple cancer cell lines including HeLa, HEK 293T, A549, MCF-7, and HT-29. This novel approach targeting RAS's post-translational prenyl modification to induce RAS degradation by employing the sequential azidation/fluorination and click reaction has been demonstrated efficiently and highly selectively, expanding PROTAC toolsets in the study of disease-relevant protein targets.
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Halogenação , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Proteínas , Proteólise , Células HeLa , Ubiquitina-Proteína LigasesRESUMO
The discovery of neuroglobin (Ngb), a brain- or neuron-specific member of the hemoglobin family, has revolutionized our understanding of brain oxygen metabolism. Currently, how Ngb plays such a role remains far from clear. Here, we report a novel mechanism by which Ngb might facilitate neuronal oxygenation upon hypoxia or anemia. We found that Ngb was present in, co-localized to, and co-migrated with mitochondria in the cell body and neurites of neurons. Hypoxia induced a sudden and prominent migration of Ngb towards the cytoplasmic membrane (CM) or cell surface in living neurons, and this was accompanied by the mitochondria. In vivo, hypotonic and anemic hypoxia induced a reversible Ngb migration toward the CM in cerebral cortical neurons in rat brains but did not alter the expression level of Ngb or its cytoplasm/mitochondria ratio. Knock-down of Ngb by RNA interference significantly diminished respiratory succinate dehydrogenase (SDH) and ATPase activity in neuronal N2a cells. Over-expression of Ngb enhanced SDH activity in N2a cells upon hypoxia. Mutation of Ngb at its oxygen-binding site (His64) significantly increased SDH activity and reduced ATPase activity in N2a cells. Taken together, Ngb was physically and functionally linked to mitochondria. In response to an insufficient oxygen supply, Ngb migrated towards the source of oxygen to facilitate neuronal oxygenation. This novel mechanism of neuronal respiration provides new insights into the understanding and treatment of neurological diseases such as stroke and Alzheimer's disease and diseases that cause hypoxia in the brain such as anemia.
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Anemia , Globinas , Ratos , Animais , Neuroglobina/metabolismo , Globinas/genética , Globinas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Hipóxia/metabolismo , Encéfalo/metabolismo , Oxigênio , Anemia/metabolismo , Adenosina Trifosfatases/metabolismoRESUMO
[This corrects the article DOI: 10.3389/fsurg.2022.995194.].
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The polysaccharides found in Lentinula edodes have a variety of medicinal properties, such as anti-tumor and anti-viral effects, but their content in L. edodes sporophores is very low. In this study, Fe2+ was added to the liquid fermentation medium of L. edodes to analyze its effects on mycelial growth, polysaccharide and enzyme production, gene expression, and the activities of enzymes involved in polysaccharide biosynthesis, and in vitro antioxidation of polysaccharides. The results showed that when 200 mg/L of Fe2+ was added, with 7 days of shaking at 150 rpm and 3 days of static culture, the biomass reached its highest value (0.28 mg/50 mL) 50 days after the addition of Fe2+. Besides, Fe2+ addition also enhanced intracellular polysaccharide (IPS) and exopolysaccharide (EPS) productions, the levels of which were 2.98- and 1.79-fold higher than the control. The activities of the enzymes involved in polysaccharides biosynthesis, including phosphoglucomutase (PGM), phosphoglucose isomerase (PGI), and UDPG-pyrophosphorylase (UGP) were also increased under Fe2+ addition. Maximum PGI activity reached 1525.20 U/mg 30 days after Fe2+ addition, whereas PGM and UGP activities reached 3607.05 U/mg and 3823.27 U/mg 60 days after Fe2+ addition, respectively. The Pearson correlation coefficient showed a strong correlation (p < 0.01) between IPS production and PGM and UGP activities. The corresponding coding genes of the three enzymes were also upregulated. When evaluating the in vitro antioxidant activities of polysaccharides, EPS from all Fe2+-treated cultures exhibited significantly better capacity (p < 0.05) for scavenging -OH radicals. The results of the two-way ANOVA indicated that the abilities of polysaccharides to scavenge O2− radicals were significantly (p < 0.01) affected by Fe2+ concentration and incubation time. These results indicated that the addition of iron provided a good way to achieve desirable biomass, polysaccharide production, and the in vitro antioxidation of polysaccharides from L. edodes.
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Background: Traditional open gastric cancer surgery has evolved from porous to reduced-hole, single-hole, or even natural cavity surgery to laparoscopic surgery, due to the continuous development of minimally invasive concepts and medical technologies, as well as awareness for the concept of rapid recovery. Conventional laparoscopic radical gastrectomy is quite mature in age at the moment, but how to progress to minimally invasive surgery without increasing the difficulty of surgery while ensuring clinical safety and feasibility is worth further investigation. Therefore, the clinical safety and feasibility of reduced port laparoscopic radical gastrectomy were assessed in this study. Methods: Information on the clinical data of patients undergoing laparoscopic radical gastric cancer surgery in a single centre between May 2020 and May 2022 was collected, and a total of 232 patients were included in this study according to the study protocol design. The clinical data of 232 patients with gastric cancer treated by two different surgical methods, namely, reduced port laparoscopic surgery (RPLS) or conventional laparoscopic surgery (CLS), were retrospectively analysed. The intraoperative indices, postoperative pathological indices, and short-term postoperative complications (within 30 days) of the two different surgical methods were evaluated, as well as the surgical methods' feasibility and short-term postoperative recovery effect. Results: There was no significant difference between the general data of patients with RPLS and CLS (P > 0.05). Compared with CLSG, the operation time, digestive tract reconstruction time and lymph node dissection time of RPLSG are shorter. The intraoperative blood loss was less, and the incision was minimally invasive (P < 0.05). In the short-term postoperative effect, the level of white blood cell count on the first day, the time of getting out of bed, the time of removing drainage tube, the time of hospitalization and the VAS of pain on the first, third and fifth days after operation, RPLSG was obviously superior to CLSG (P < 0.05). There was no significant difference between RPLSG and CLSG in terms of pathological indices (P > 0.05). Conclusions: The treatment of gastric cancer with RPLS has good safety, feasibility and short-term postoperative effects, which is in line with the implementation of the modern concept of rapid rehabilitation surgery.