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BACKGROUND: Hematoma clearance is crucial for treating intracerebral hemorrhage (ICH). Currently, there is a lack of pharmacological therapy aimed at promoting hematoma absorption. Meningeal lymphatic system, as a drain of brain, is a potential therapeutic approach in ICH. Panax Notoginseng Saponins (PNS), proven to promote lymphangiogenesis in periphery, effectively reduces hematoma in ICH patients. However, the potential pharmacological effect of PNS on meningeal lymphatic vessels (MLVs) remains unknown. PURPOSE: In this study, we aimed to investigate the impact of PNS on the meningeal lymphatic system and ICH. METHODS: The collagenase-ICH model was conducted to investigate the effect of PNS. Behavioral tests, including modified neurological severity score (mNSS) and foot-fault test, and hematoma volume were used to estimate the neurological function and curative effect. The structure and drainage function of MLVs was detected by immunohistochemical staining. Visudyne intracisternal magna injection combined with red laser photoconversion was performed to ablate MLVs. RNA-sequencing was used to obtain mRNA profiles for mechanistic investigation. RESULTS: The meningeal lymphatic drainage function was enhanced after ICH on day 14 without obvious lymphangiogenesis. Additionally, PNS further facilitated the process of drain with simultaneously inducing lymphangiogenesis. Moreover, ablation of MLVs by photoconverting of visudyne significantly blocked the benefits of neurological deficits improvement and hematoma absorption conducted by PNS. Furthermore, RNA-sequencing revealed that PNS regulated axonogenesis and inflammation, relying on the intact MLVs. In which, solute carrier family 17 member 7 (Slc17a7) and tumor necrosis factor (Tnf) were identified as bottleneck and hub nodes of the protein-protein interaction network of target genes, respectively. CONCLUSION: PNS might be effective for ICH treatment by enhancing lymphangiogenesis and the meningeal lymphatic drainage function, thereby attenuating inflammation and promoting neurological recovery. The role of PNS in regulation of MLVs was investigated for the first time. This study provides a novel insight for PNS in the medical therapy of ICH.
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The recent success of RFdiffusion, a method for protein structure design with a denoising diffusion probabilistic model, has relied on fine-tuning the RoseTTAFold structure prediction network for protein backbone denoising. Here, we introduce SCUBA-diffusion (SCUBA-D), a protein backbone denoising diffusion probabilistic model freshly trained by considering co-diffusion of sequence representation to enhance model regularization and adversarial losses to minimize data-out-of-distribution errors. While matching the performance of the pretrained RoseTTAFold-based RFdiffusion in generating experimentally realizable protein structures, SCUBA-D readily generates protein structures with not-yet-observed overall folds that are different from those predictable with RoseTTAFold. The accuracy of SCUBA-D was confirmed by the X-ray structures of 16 designed proteins and a protein complex, and by experiments validating designed heme-binding proteins and Ras-binding proteins. Our work shows that deep generative models of images or texts can be fruitfully extended to complex physical objects like protein structures by addressing outstanding issues such as the data-out-of-distribution errors.
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BACKGROUND: Cocktails containing glucocorticoids for local infiltration analgesia (LIA) are highly advocated and effective in managing pain in total joint arthroplasty (TJA). However, it remains ambiguous whether this protocol maintains its safety and efficacy in the treatment of periprosthetic joint infection (PJI), a devastating complication of TJA. METHODS: A retrospective study was conducted on 299 single-stage revision cases for PJI spanning the years 2010 to 2021. Of these, 127 received LIAs containing high-dose compound betamethasone (CB) were termed the CB group, and the other 172 were termed the non-CB group. The rates of re-infection and other postoperative complications, along with postoperative visual analog scale (VAS) scores, and opioid consumption were compared. RESULTS: During minimum 2-year follow-up, there was no significant difference in the re-infection rate between the non-CB and CB groups (9.3 versus 8.7%; P = 0.85), consistent within the subsets of hip (8.4 versus 4.5%; P = 0.51) and knee (10.4 versus 13.3%; P = 0.60) PJIs individually. The administration of high-dose CB was neither an independent risk factor for reinfection (P > 0.05; 95% CI [confidence interval] including 1) nor was it associated with the occurrence of reinfection (P > 0.05). The incidence of postoperative nausea and vomiting (PONV) was significantly lower in the CB group (P < 0.05). In the first 48-hour postoperative period, the CB group exhibited lower mean scores in both resting and movement VAS evaluations (P < 0.05). For knees, the movement VAS scores of the CB group remained lower even at 72 hours post-surgery (P < 0.001). Furthermore, within the first 72 hours post-surgery, the CB group required less additional opioid analgesics than the non-CB group (P < 0.05). CONCLUSIONS: A LIA with a high-dose CB reduces postoperative pain, opioid consumption, and the incidence of PONV following a single-stage revision without affecting reinfection and other complication rates.
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Racial differences in healthcare access (HCA) may contribute to disparities in ovarian cancer (OC) survival. We used structural equation models (SEM) to examine associations between race and HCA domains (affordability, availability, accessibility) in relation to overall and OC-specific mortality. Non-Hispanic (NH)-Black and non-Black (Hispanic, NH-White) women diagnosed with OC in 2008-2015 were identified from SEER-Medicare. Cox proportional hazards regression was used to conduct mediation analysis for associations between race and HCA domains with overall and OC-specific mortality. SEM models adjusting for demographic and clinical covariates were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). A total of 4,629 eligible OC patients were identified, including 255 (5.5%) patients who were NH-Black. In SEM adjusting for demographic, clinical, and HCA latent variables, there was a total effect of NH-Black race on overall (HR: 1.11, 95% CI: 1.03,1.19) and OC-specific mortality (HR: 1.16, 95% CI: 1.08, 1.24), which was primarily driven by a direct effect. There was a modest indirect association between NH-Black race and mortality through decreased treatment receipt, though not through HCA. There is a need for studies investigating additional social and biological mechanisms that contribute to worse cancer survival among NH-Black patients.
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BACKGROUND: Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) enhances tumor immune escape and leads to tumor growth. PURPOSE: To investigate the expression of Siglec-15 in diffuse gliomas and its correlation with tumor magnetic resonance imaging (MRI) features. MATERIAL AND METHODS: This study included 57 patients with gliomas. Morphological MRI features, including the largest tumor diameter, enhancement category, location, calcification, cysts, and hemorrhage, were visually rated. Apparent diffusion coefficient (ADC) values were calculated in tumor region. MRI morphologic features and ADC were compared between patients with positive and negative Siglec-15 expression. Receiver operating characteristic (ROC) curves were further constructed to assess the diagnostic performance. RESULTS: Siglec-15 was expressed in immunocytes, such as macrophages in the peritumoral area. Siglec-15 expression was positive in 20/57 (35.09%) patients, with higher expression in patients with IDH-mutant gliomas and lower grade gliomas. The tumor diameter was significantly smaller in patients with positive Siglec-15 expression than in those with negative expression for all patients (P = 0.017) and for patients with IDH-mutant gliomas (P = 0.020). Moreover, ADC values of the tumor were significantly higher in patients with positive Siglec-15 expression than in those with negative expression for all patients (P = 0.027). The areas under the ROC curve (AUCs) of the diameter and ADC were 0.702 and 0.686, respectively. A combination of these two parameters generated an improved AUC of 0.762. CONCLUSION: Siglec-15 was expressed in immunocytes such as macrophages in the peritumoral area, with a positive rate of 35.09%. Positive Siglec-15 expression in diffuse gliomas was correlated with smaller tumor size and higher ADC values.
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The Chinese mitten crab (Eriocheir sinensis) holds significant importance as a popular aquaculture food source; however, there are concerns about its potential contamination with polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs) from both food and aquatic environment. To assess the associated health risks and identify potential sources of contamination in crabs, a comprehensive investigation was conducted, including a total of 70 samples from the crab food web. The results demonstrated that crabs predominantly exhibited elevated concentrations of PCBs and dl-PCBs, with mean concentrations of 12 207 ± 11 962 pg g-1 and 554 ± 203 pg g-1, respectively, while PCDD/Fs concentrations were comparatively lower at 20 ± 17 pg g-1. The accumulation of PCBs in crabs significantly surpassed that of PCDD/Fs. The material balance of PCDD/Fs and PCBs in the crab food web was estimated, indicating that sediments and feeds likely constitute the two primary sources of PCDD/Fs and PCBs in crabs. The monthly intake of PCDD/Fs and PCBs through crab consumption accounted for 30% of the dietary intake, which was well below the provisional tolerable monthly intake (PTMI) limit. The weekly intake of PCDD/Fs and PCBs for adults consuming one crab (100 g) does not pose health risks and the recommended weekly intake of white crabmeat and brown crabmeat is 443 g and 21 g, respectively.
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Braquiúros , Contaminação de Alimentos , Bifenilos Policlorados , Dibenzodioxinas Policloradas , Animais , Bifenilos Policlorados/análise , Braquiúros/metabolismo , Dibenzodioxinas Policloradas/análise , Contaminação de Alimentos/análise , Humanos , Dibenzofuranos Policlorados/análise , Aquicultura , Poluentes Químicos da Água/análise , Medição de Risco , Benzofuranos/análiseRESUMO
Microvasculature is essential for the continued function of cells in tissue and is fundamental in the fields of tissue engineering, organ repair and drug screening. However, the fabrication of microvasculature is still challenging using existing strategies. Here, we developed a general PRINting Cell Embedded Sacrificial Strategy (PRINCESS) and successfully fabricated microvasculatures using degradable DNA biolubricant. This is the first demonstration of direct cell printing to fabricate microvasculature, which eliminates the need for a subsequent cell seeding process and the associated deficiencies. Utilizing the shear-thinning property of DNA hydrogels as a novel sacrificial, cell-laden biolubricant, we can print a 70-µm endothelialized microvasculature, breaking the limit of 100 µm. To our best knowledge, this is the smallest endothelialized microvasculature that has ever been bioprinted so far. In addition, the self-healing property of DNA hydrogels allows the creation of continuous branched structures. This strategy provides a new platform for constructing complex hierarchical vascular networks and offers new opportunity towards engineering thick tissues. The extremely low volume of sacrificial biolubricant paves the way for DNA hydrogels to be used in practical tissue engineering applications. The high-resolution bioprinting technique also exhibits great potential for printing lymphatics, retinas and neural networks in the future.
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Chemotherapy (CT) can significantly inhibit tumor growth, metastasis, and recurrence during cancer therapy. People have widely used platinum drugs in cancer treatment. However, as most chemotherapeutic drugs, platinum drugs still have shortcomings such as poor solubility, low cell uptake, nonspecific distribution, multidrug resistance, and adverse side effects. Therefore, we synthesized hollow copper sulfide (CuS) nanocubes with photothermal and photodynamic properties as carriers for Pt(IV) drugs. Hollow CuS nanocubes have attracted considerable interest in the field of cancer photothermal therapy (PTT) using multiple biological windows. Under near-infrared (NIR) laser irradiation, Cu2+ can be reduced into Cu+ in the presence of hydrogen peroxide in the tumor microenvironment. The resulting Cu+ can be used for photodynamic therapy (PDT), which can perform a Fenton-like reaction under acidic conditions (pH 5.5-6.5) and catalyze hydrogen peroxide to produce ·OH in the tumor microenvironment. In addition, compared with Pt(II) drugs, Pt(IV) drugs not only have lower systemic toxicity but also consume glutathione (GSH), thereby increasing reactive oxygen species (ROS) levels in tumor cells and effectively promoting PDT. In this study, we oxidized ethylenediamine platinum chloride to its tetravalent state, loaded the Pt(IV) complexes using hollow CuS nanocubes, and modified the surfaces of the nanoparticles with PEG to improve the EPR effect. The Pt(IV)-loaded hollow CuS nanocubes modified with PEG (Pt(IV)-CuS@PEG) are expected to be used for tumor chemo/photothermal/photodynamic therapy.
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Antineoplásicos , Cobre , Fotoquimioterapia , Cobre/química , Cobre/farmacologia , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologia , Sulfetos/química , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Platina/química , Platina/farmacologia , Portadores de Fármacos/química , Linhagem Celular Tumoral , Compostos Organoplatínicos/química , Compostos Organoplatínicos/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/uso terapêuticoRESUMO
BACKGROUND: Magnetic resonance imaging (MRI) is considered the gold standard for prostate segmentation. Computed tomography (CT)-based segmentation is prone to observer bias, potentially overestimating the prostate volume by â¼ 30 % compared to MRI. However, MRI accessibility is challenging for patients with contraindications or in rural areas globally with limited clinical resources. PURPOSE: This study investigates the possibility of achieving MRI-level prostate auto-segmentation accuracy using CT-only input via a deep learning (DL) model trained with CT-MRI registered segmentation. METHODS AND MATERIALS: A cohort of 111 definitive prostate radiotherapy patients with both CT and MRI images was retrospectively grouped into training (n = 37) and validation (n = 20) (where reference contours were derived from CT-MRI registration), and testing (n = 54) sets. Two commercial DL models were benchmarked against the reference contours in the training and validation sets. A custom DL model was incrementally retrained using the training dataset, quantitatively evaluated on the validation dataset, and qualitatively assessed by two different physician groups on the validation and testing datasets. A contour quality assurance (QA) model, established from the proposed model on the validation dataset, was applied to the test group to identify potential errors, confirmed by human visual inspection. RESULTS: Two commercial models exhibited large deviations in the prostate apex with CT-only input (median: 0.77/0.78 for Dice similarity coefficient (DSC), and 0.80 cm/0.83 cm for 95 % directed Hausdorff Distance (HD95), respectively). The proposed model demonstrated superior geometric similarity compared to commercial models, particularly in the apex region, with improvements of 0.05/0.17 cm and 0.06/0.25 cm in median DSC/HD95, respectively. Physician evaluation on MRI-CT registration data rated 69 %-78 % of the proposed model's contours as clinically acceptable without modifications. Additionally, 73 % of cases flagged by the contour quality assurance (QA) model were confirmed via visual inspection. CONCLUSIONS: The proposed incremental learning strategy based on CT-MRI registration information enhances prostate segmentation accuracy when MRI availability is limited clinically.
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BACKGROUND: Xuefu Zhuyu decoction (XFZYD) has been extensively utilized to treat traumatic brain injury (TBI). However, the bioactive compounds and the underlying mechanisms have not yet been elucidated. OBJECTIVES: This study aimed to investigate the bioactive constituents of XFYZD that are absorbed in the blood and the mechanisms in treating TBI. METHODS: The study presents an integrated strategy in three steps to investigate the material basis and pharmacological mechanisms of XFZYD. The first step involves: (1) performing metabolomics analysis of XFZYD to obtain the main functions and targets; (2) screening the blood-entry ingredients and targets of XFZYD from databases; (3) obtaining the potential components targeting the key functions by integrated analysis of metabolomics and network pharmacology. The second step involves screening pharmacological effects with active ingredients in vitro. In the third step, the effects of the top active compound were validated in vivo, and the mechanisms were explored by protein antagonist experiments. RESULTS: Metabolomics analysis revealed that XFZYD treated TBI mice mainly through affecting the functions of blood vessels. We screened 62 blood-entry ingredients of XFZYD by network pharmacology. Then, we focused on 39 blood-entry ingredients related to vascular genes enriched by XFZYD-responsive metabolites. Performing the natural products library, we verified that hydroxysafflor yellow A (HSYA), vanillin, ligustilide, paeoniflorin, and other substances promoted endothelial cell proliferation significantly compared to the control group. Among them, the efficacy of HSYA was superior. Further animal studies demonstrated that HSYA treatment alleviated neurological dysfunction in TBI mice by mNSS and foot fault test, and decreased neuronal damage by HE, nissl, and TUNEL staining. HSYA increased the density of cerebral microvessels, raised the expression of angiogenesis marker proteins VEGFA and CD34, and activated the PI3K/Akt/mTOR signaling pathway significantly. The angiogenic effects disappeared after the intervention of PI3K antagonist LY294002. CONCLUSION: By applying a novel strategy of integrating network pharmacology of constituents absorbed in blood with metabolomics, the research screened HSYA as one of the top bioactive constituents of XFZYD, which stimulates angiogenesis by activating the PI3K/Akt/mTOR signaling pathway after TBI.
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Background: Carcinosarcoma is a rare esophageal tumor, accounting for approximately 0.27-2.8% of malignant esophageal tumors. This study aims to investigate the clinical pathological characteristics, surgical treatment outcomes, and analysis of prognostic factors in esophageal carcinosarcoma (ECS). Methods: Clinical data from sixteen patients diagnosed with esophageal sarcomatoid carcinoma who underwent surgical interventions were retrospectively analyzed. Clinical and pathological features, treatment modalities, and postoperative outcomes were systematically examined. Results: Out of the 1261 patients who underwent surgical treatment for esophageal cancer, 16 cases were pathologically confirmed as carcinosarcoma. Among them, two underwent neoadjuvant chemotherapy, six received postoperative chemotherapy. Carcinosarcomas predominantly occurred in the middle (43.75%) and lower (50%) segments of the esophagus. Among the 16 cases, 10 presented as polypoid, 4 as ulcerative, and 2 as medullary types. Microscopic examination revealed coexistence and transitional transitions between sarcomatous and carcinoma components. Pathological staging showed 5 cases in stage T1, 2 in stage T2, and 9 in stage T3, with lymph node metastasis observed in 8 cases (50%). TNM staging revealed 2 cases in stage I, 9 in stage II, and 5 in stage III. The overall 1, 3, and 5-year survival rates were 86.67%, 62.5%, and 57.14%, respectively. Univariate analysis indicated that pathological N staging influenced survival rates, while multivariate analysis demonstrated that pathological N staging was an independent prognostic factor. Conclusions: Carcinosarcoma is a rare esophageal tumor, accounting for approximately 0.27-2.8% of malignant esophageal tumors. Histologically, the biphasic pattern is a crucial diagnostic feature, although the carcinomatous component may not always be evident, especially in limited biopsies, leading to potential misclassification as pure sarcoma or squamous cell carcinoma. Despite its large volume and cellular atypia, carcinosarcoma carries a favorable prognosis. Complete surgical resection of the tumor and regional lymph node dissection is the preferred treatment approach for esophageal carcinosarcoma.
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Objective: To evaluate the association between musculoskeletal pain and incident sarcopenia and further explore the mediating effect of depressive symptoms among middle-aged and older Chinese adults. Methods: Using the data from the China Health and Retirement Longitudinal Study 2011 and 2015, we included 12,788 participants in the cross-sectional analysis and 8,322 for the longitudinal analysis. Musculoskeletal pains located in the neck, back, waist, shoulder, arm, wrist, leg, knee, and ankle were self-reported at baseline and follow-up. The diagnosis criteria of sarcopenia was based on the Asian Working Group for Sarcopenia 2019. Multivariable logistic regression models were used to evaluate the association between musculoskeletal pain, and the Karlson-Holm-Breen (KHB) method was used to explore the mediating effect of depressive symptoms. Results: Over the 4-year follow-up, 445 participants were identified with incident sarcopenia. In the longitudinal analysis, participants with baseline musculoskeletal pain (adjusted odds ratio (OR): 1.37, 95% confidence interval (CI): 1.07-1.76), persistent musculoskeletal pain (OR:1.68, 95%CI: 1.28-2.24), and persistent waist pain (OR:1.46, 95%CI: 1.04-2.03) were significantly associated with increased the risk of incident sarcopenia. Furthermore, depressive symptoms were found to partially mediate the association between musculoskeletal pain and incident sarcopenia. Conclusion: Persistent musculoskeletal pain, especially in waist area, was positively associated with a higher risk of sarcopenia among the middle-aged and older Chinese. Depressive symptoms played a partial mediating role in this association.
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Depressão , Dor Musculoesquelética , Sarcopenia , Humanos , Masculino , Feminino , Sarcopenia/epidemiologia , China/epidemiologia , Depressão/epidemiologia , Pessoa de Meia-Idade , Dor Musculoesquelética/epidemiologia , Estudos Transversais , Estudos Longitudinais , Idoso , Fatores de Risco , IncidênciaRESUMO
Creating CâC bonds as "weak" sites in the stable C-C chains of polyethylene (PE) is an appealing strategy to promote sustainable development of the polyolefin industry. Compared to methods, such as dehydrogenation and postpolymerization modification, the copolymerization of ethylene (E) and butadiene (BD) should be a convenient and direct approach to introduce CâC bonds in PE, whereas it encounters problems in controlling the composition and regularity of the copolymer due to the mismatched activities and mechanisms between the two monomers. Herein, we report by employing the amidinate gadolinium complex, controllable E/BD copolymerization was achieved, where BD was incorporated in the uniformly discrete 1,4 mode. The obtained copolymer possesses the same physical, mechanical, processing, and antioxygen (aging at 100 °C for 28 days) properties as commercial high-density-PE, which, strikingly, were degraded by CâC bonds into α,ω-telechelic oligomers with narrow distribution. These degraded functional products were transferred to compatibilizers via atom-transfer radical polymerization or immortal ring-opening polymerization, achieving upcycling.
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Eutrophication has become one of the greatest threats to aquatic ecosystems. The release of phosphorus (P) from sediments exerts a critical role on eutrophication level. Both manganese (Mn) and iron (Fe), sensitive to redox conditions, own strong affinity for P. Numerous works have demonstrated that Fe was a key factor to drive P cycle in sediments. However, the role of Mn on P mobilization remains largely unexplored. Herein, the mechanism of P mobilization driven by Mn were investigated in a seasonal anoxic reservoir. Diffusive gradients in thin films (DGT) results, from both field investigations and laboratory incubations, showed P was synchronously distributed and significantly positive correlated (r2 ≥ 0.40, p < 0.01) with Mn, suggested that P cycle was associated with Mn. X-ray photoelectron spectroscopy (XPS) results showed that in the outer layers at the top 1 cm sediment pellet the contents of Mn and P occurred significantly synchronize changed, while that of Fe remains virtually unchanged when oxygen conditions changed. This demonstrated that Mn is likely to be the key factor affect P cycle. Most importantly, the relative content of Mn(III) changed the most (≈20 %) interpreted that Mn(III) is the key Mn species dominants the P mobilization. Furthermore, Dual-Beam scanning electron microscope (DB-SEM) maps clearly showed the co-enrichment of P and Mn in oxic sediments, confirmed P was mainly hosted by Mn minerals. In contrast, the random distributions and weak or negative correlations between P and Fe implied that P cycle was decouple with Fe, this resulted from that Fe was almost deposited as inert Fe fractions (>99.2 %) in reducing sediments. This study significantly expanded our knowledge on the geochemical behavior of P influenced by Mn in aquatic sediments.
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Trace elemental iron is an essential nutrient that participates in diverse metabolic processes. Dysregulation of cellular iron homeostasis, both iron deficiency and iron overload, is detrimental and tightly associated with disease pathogenesis. IRPs-IREs system is located at the center for iron homeostasis regulation. Additionally, ferritinophagy, the autophagy-dependent ferritin catabolism for iron recycling, is emerging as a novel mechanism for iron homeostasis regulation. It is still unclear whether IRPs-IREs system and ferritinophagy are synergistic or redundant in determining iron homeostasis. Here we report that IRP2, but not IRP1, is indispensable for ferritinophagy in response to iron depletion. Mechanistically, IRP2 ablation results in compromised AMPK activation and defective ATG9A endosomal trafficking, leading to the decreased engulfment of NCOA4-ferritin complex by endosomes and the subsequent dysregulated endosomal microferritinophagy. Moreover, this defective endosomal microferritinophagy exacerbates DNA damage and reduces colony formation in IRP2-depleted cells. Collectively, this study expands the physiological function of IRP2 in endosomal microferritinophagy and highlights potential crosstalk between IRPs-IREs and ferritinophagy in manipulating iron homeostasis.
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Proteínas Relacionadas à Autofagia , Autofagia , Dano ao DNA , Endossomos , Ferritinas , Ferro , Humanos , Ferritinas/metabolismo , Ferritinas/genética , Ferro/metabolismo , Proteínas Relacionadas à Autofagia/metabolismo , Proteínas Relacionadas à Autofagia/genética , Endossomos/metabolismo , Proteínas de Membrana Lisossomal/metabolismo , Proteínas de Membrana Lisossomal/genética , Coativadores de Receptor Nuclear/metabolismo , Coativadores de Receptor Nuclear/genética , Transporte Proteico , Reparo do DNA , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Camundongos , Animais , Homeostase , Células HeLa , Proteínas de Transporte VesicularRESUMO
Phenols are the widely detected contaminants in the aquatic environment. Pyrogenic carbon (PyC) can mediate phenols degradation, but the specific properties of PyC or phenols influencing this reaction remain unknown. The present study investigated the kinetic process and mechanism of removal of various phenols by different PyC in aqueous phase system. To avoid the impact of the accumulated degradation byproducts on the overall reaction, we conducted a short-term experiment, quantified adsorption and degradation, and obtained reaction rate constants using a two-compartment first-order kinetics model. The adsorption rate constants (ka) of phenols by PyC were 10-220 times higher than degradation rate constants (kd), and they were positively correlated. Interestingly, no correlation was found between kd and common PyC properties, including functional groups, electron transfer capacities, and surface properties. Phenols were primarily attacked by â¢OH in the adsorbed phase. But neither the instantly trapped â¢OH, nor the accumulated â¢OH could explain phenol degradation. Chemical redox titration revealed that the electron transfer parameters, such as the electron donating rate constant (kED) of PyC, correlated well with kd (r>0.87, P < 0.05) of phenols. Analysis of 13 phenols showed that Egap and ELUMO negatively correlated with their kd, confirming the importance of the electronic properties of phenols to their degradation kinetics. This study highlights the importance of PyC electron transfer kinetics parameters for phenols degradation and manipulation of PyC electron transfer rate may accelerate organic pollutant removal, which contributes to a deeper understanding of the environmental behavior and application of PyC systems.
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Carbono , Fenóis , Poluentes Químicos da Água , Fenóis/química , Poluentes Químicos da Água/química , Cinética , Adsorção , Carbono/química , ElétronsRESUMO
Callose, found in the cell walls of higher plants such as ß-1,3-glucan with ß-1,6 branches, is pivotal for both plant development and responses to biotic and abiotic stressors. Plasmodesmata (PD), membranous channels linking the cytoplasm, plasma membrane, and endoplasmic reticulum of adjacent cells, facilitate molecular transport, crucial for developmental and physiological processes. The regulation of both the structural and transport functions of PD is intricate. The accumulation of callose in the PD neck is particularly significant for the regulation of PD permeability. This callose deposition, occurring at a specific site of pathogenic incursion, decelerates the invasion and proliferation of pathogens by reducing the PD pore size. Scholarly investigations over the past two decades have illuminated pathogen-induced callose deposition and the ensuing PD regulation. This gradual understanding reveals the complex regulatory interactions governing defense-related callose accumulation and protein-mediated PD regulation, underscoring its role in plant defense. This review systematically outlines callose accumulation mechanisms and enzymatic regulation in plant defense and discusses PD's varied participation against viral, fungal, and bacterial infestations. It scrutinizes callose-induced structural changes in PD, highlighting their implications for plant immunity. This review emphasizes dynamic callose calibration in PD constrictions and elucidates the implications and potential challenges of this intricate defense mechanism, integral to the plant's immune system.
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Objective: This study aimed to characterize multivariate trajectories of blood pressure [systolic blood pressure (SBP) and diastolic blood pressure (DBP)] jointly and examine their impact on incident cardiovascular disease (CVD) among a Chinese elderly medical examination population. Methods: A total of 13,504 individuals without CVD during 2018-2020 were included from the Chinese geriatric physical examination cohort study. The group-based trajectory model was used to construct multi-trajectories of systolic blood pressure and diastolic blood pressure. The primary outcome was the incidence of the first CVD events, consisting of stroke and coronary heart diseases, in 2021. The Cox proportional hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between BP multi-trajectories and incident CVD events. Results: We identified four blood pressure (BP) subclasses, summarized by their SBP and DBP levels from low to high as class 1 (7.16%), class 2 (55.17%), class 3 (32.26%), and class 4 (5.41%). In 2021, we documented 890 incident CVD events. Compared with participants in class 1, adjusted HRs were 1.56 (95% CI: 1.12-2.19) for class 2, 1.75 (95% CI: 1.24-2.47) for class 3, and 1.88 (95% CI: 1.24-2.85) for class 4 after adjustment for demographics, health behaviors, and metabolic index. Individuals aged 65â years and above with higher levels of BP trajectories had higher risks of CVD events in China. Conclusions: Individuals with higher levels of both SBP and DBP trajectories over time were associated with an increased risk of incident CVD in the Chinese elderly population.
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Cataracts are characterized as a disease affecting lens opacity. Endoplasmic reticulum (ER) stress can cause lens epithelial cell (LEC) dysfunction, affecting normal lens transparency and function, but the role of Tribbles 3 (TRB3), an inducible gene of ER stress, in cataracts is poorly understood. This study explored how TRB3 promotes cataract progression through ER stress. We administered a subcutaneous injection of sodium selenite at a dosage of 3.46 mg/kg to rats to create an animal model of cataracts. Additionally, we exposed rat LEC cells to 0.01 µM tunicamycin (TM) for 24 h to establish a cell model of ER stress. The detection of related genes and proteins was performed via RTâqPCR and Western blot techniques. Flow cytometry, along with JC-1, TUNEL, and HE staining, was employed to assess damage to cells and lens tissues. This study revealed that TRB3 was abnormally highly expressed in both a cataract rat model and an ER stress cell model. Knocking down TRB3 has a similar effect as treatment with an ER stress inhibitor, effectively reversing the ER stress and apoptosis induced by TM. This effect includes increasing the mitochondrial membrane potential in LEC cells, lowering reactive oxygen species (ROS) levels, increasing ATP production, suppressing the expression of the apoptosis-related proteins Bax and C-caspase-3, increasing Bcl-2 expression, and decreasing apoptosis. Furthermore, TRB3 knockdown improved the pathological conditions of rat lenses and inhibited mitochondrial dysfunction and cell apoptosis to relieve the development of cataracts in rats. Mechanistically, CHOP promotes the expression of TRB3 by binding to the TRB3 promoter, thereby activating ER stress, leading to mitochondrial dysfunction and cell apoptosis in LEC cells and accelerating the development of cataracts. According to our findings, targeting TRB3 expression inhibition could emerge as a novel approach for cataract therapy.
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Current international optical science research focuses on the non-visual effects of lighting on human cognition, mood, and biological rhythms to enhance overall well-being. Nocturnal roadway lighting, in particular, has a substantial impact on drivers' physiological and psychological states, influencing behavior and safety. This study investigates the non-visual effects of correlated color temperature (CCT: 3000K vs. 4000K vs. 5000K) and illuminance levels (20 lx vs. 30 lx) of urban motor vehicle road lighting on driver alertness during various driving tasks. Conducted between 19:00 and 20:30, the experiments utilized a human-vehicle-light simulation platform. EEG (ß waves), reaction time, and subjective evaluations using the Karolinska Sleepiness Scale (KSS) were measured. The results indicated that the interaction between CCT and illuminance, as well as between CCT and task type, significantly influenced driver alertness. However, no significant effect of CCT and illuminance on reaction time was observed. The findings suggest that higher illuminance (30 lx) combined with medium CCT (4000K) effectively reduces reaction time. This investigation enriches related research, provides valuable reference for future studies, and enhances understanding of the mechanisms of lighting's influence on driver alertness. Moreover, the findings have significant implications for optimizing the design of urban road lighting.