RESUMO
Cadmium (Cd) and lead (Pb) exposure have been identified as risk factors for Helicobacter pylori seropositivity, possibly due to the immune suppression by Cd and Pb. Physical activity (PA) can induce an immune response. However, whether PA can reduce the effect of Cd and Pb on H pylori infection remains elusive. This study aims to investigate the association of blood Cd and Pb levels with H pylori infection and explore the intermediary effects of PA. This cross-sectional survey was conducted using the National Health and Nutrition Examination Survey (NHANES) of the 1999 to 2000 cycle (nâ =â 9965). Participants without clear serological testing data, or absent in PA, blood Cd, and Pb information were excluded. Collinearity analysis was performed to remove the variables with high collinearity. Restricted cubic spline curve analysis was adopted to assess the nonlinear association of Cd and Pb with H pylori infection. The logistic regression analysis, generalized linear models, sensitivity analysis, and P for trend test were used to further analyze their relationship. Then, we analyzed the association of Cd and Pb with H pylori infection in 2 PA groups. Totally 3638 participants were divided into H pylori-negative (nâ =â 2545) and H pylori-positive group (nâ =â 1093). Pb exhibited a linear relationship but Cd had a nonlinear relationship with H pylori infection. Besides, the elevation of Cd and Pb both independently predicted H pylori infection after adjusting various variables (Pâ <â .05). The robust relationship was confirmed by the P for trend test (P for trendâ <â .05). Under Cd exposure, the risk of H pylori infection was lower in the active PA group than in the inactive group (Pâ <â .05). A reverse result was found under the Pb exposure (Pâ <â .05). Exposure to Cd and Pb are positively linked to H pylori infection. PA may alleviate the effect of Cd on H pylori infection but may enhance H pylori infection under Pb exposure. Therefore, PA should be recommended in the appropriate season or region.
Assuntos
Cádmio , Exercício Físico , Infecções por Helicobacter , Helicobacter pylori , Chumbo , Inquéritos Nutricionais , Humanos , Infecções por Helicobacter/sangue , Infecções por Helicobacter/epidemiologia , Cádmio/sangue , Chumbo/sangue , Estudos Transversais , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Exercício Físico/fisiologia , Fatores de RiscoRESUMO
Background: The efficacy of targeted therapy for colorectal cancer (CRC) is affected by hub genes of epidermal growth factor receptor (EGFR) signaling pathways, such as KRAS. Immune cell infiltration may lead to gene mutation, but the relationship between KRAS status and peripheral immune-inflammatory indices has not been clarified in CRC. Methods: Clinical records of CRC patients were collected. The relationship between KRAS status and clinicopathological characteristics, peripheral immune-inflammatory indices (pan-immune inflammation value (PIV) (monocyte×neutrophil×platelet/lymphocyte), systemic immune inflammation index (SII) (platelet×neutrophil/lymphocyte), and system inflammation response index (SIRI) (monocyte×neutrophil/lymphocyte)) were analyzed. Results: 1033 CRC patients were collected, there were 514 (49.8%) patients with KRAS wild-type and 519 (50.2%) with KRAS mutation. Patients with KRAS mutation had higher proportions of female, III-IV stage, and lymph node metastasis and lower proportion of low grade of tumor budding (the presence of single tumor cells or small clusters of up to 5 cells in mesenchyma at the front of tumor invasion) than those with KRAS wild-type. The PIV, SII, and SIRI levels in KRAS mutation patients were significantly higher than those in KRAS wild-type patients. The proportion of aged ≥65 years old, dMMR, distant metastasis, and KRAS mutation were high in patients with high PIV, SII, and SIRI levels. Logistic regression analysis showed that non-low grade of tumor budding (odds ratio (OR): 1.970, 95% confidence interval (CI): 1.287-3.016, p=0.002), and high SII level (≥807.81 vs <807.81, OR: 1.915, 95% CI: 1.120-3.272, p=0.018) were independently associated with KRAS mutation. Conclusion: Non-low grade of tumor budding, and high SII level were independently associated with KRAS mutation in CRC. It provides additional references for diagnosis and treatment options for patients with CRC.
RESUMO
Temozolomide (TMZ) resistance is one of the major reasons for poor prognosis in patients with glioblastoma (GBM). Long noncoding RNAs (lncRNAs) are involved in multiple biological processes, including TMZ resistance. Linc00942 is a potential regulator of TMZ sensitivity in GBM cells is shown previously. However, the underlying mechanism of TMZ resistance induced by Linc00942 is unknown. In this study, the sequence of Linc00942 by rapid amplification of cDNA ends assay in TMZ-resistant GBM cells is identified and confirmed that Linc00942 contributes to self-renewal and TMZ resistance in GBM cells. Chromatin isolation by RNA purification followed by mass spectrometry (ChIRP-MS) and followed by Western blotting (ChIRP-WB) assays shows that Linc00492 interacted with TPI1 and PKM2, subsequently promoting their phosphorylation, dimerization, and nuclear translocation. The interaction of Linc00942 with TPI1 and PKM2 leads to increased acetylation of H3K4 and activation of the STAT3/P300 axis, resulting in the marked transcriptional activation of SOX9. Moreover, the knockdown of SOX9 reversed TMZ resistance induced by Linc00492 both in vitro and in vivo. In summary, Linc00942 strongly promotes SOX9 expression by interacting with TPI1 and PKM2 is found, thereby driving self-renewal and TMZ resistance in GBM cells. These findings suggest potential combined therapeutic strategies to overcome TMZ resistance in patients with GBM.
RESUMO
BACKGROUND AND PURPOSE: Fast and automated generation of treatment plans is desirable for magnetic resonance imaging (MRI)-guided adaptive radiotherapy (MRIgART). This study proposed a novel patient-specific auto-planning method and validated its feasibility in improving the existing online planning workflow. MATERIALS AND METHODS: Data from 40 patients with prostate cancer were collected retrospectively. A patient-specific auto-planning method was proposed to generate adaptive treatment plans. First, a population dose-prediction model (M0) was trained using data from previous patients. Second, a patient-specific model (Mps) was created for each new patient by fine-tuning M0 with the patient's data. Finally, an auto plan was optimized using the parameters derived from the predicted dose distribution by Mps. The auto plans were compared with manual plans in terms of plan quality, efficiency, dosimetric verification, and clinical evaluation. RESULTS: The auto plans improved target coverage, reduced irradiation to the rectum, and provided comparable protection to other organs-at-risk. Target coverage for the planning target volume (+0.61 %, P = 0.023) and clinical target volume 4000 (+1.60 %, P < 0.001) increased. V2900cGy (-1.06 %, P = 0.004) and V1810cGy (-2.49 %, P < 0.001) to the rectal wall and V1810cGy (-2.82 %, P = 0.012) to the rectum were significantly reduced. The auto plans required less planning time (-3.92 min, P = 0.001), monitor units (-46.48, P = 0.003), and delivery time (-0.26 min, P = 0.004), and their gamma pass rates (3 %/2 mm) were higher (+0.47 %, P = 0.014). CONCLUSION: The proposed patient-specific auto-planning method demonstrated a robust level of automation and was able to generate high-quality treatment plans in less time for MRIgART in prostate cancer.
Assuntos
Imageamento por Ressonância Magnética , Neoplasias da Próstata , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia Guiada por Imagem , Humanos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Masculino , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/métodos , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Órgãos em Risco/efeitos da radiaçãoRESUMO
Constructing bird habitat networks (BHNs) is crucial for maintaining the health and service equilibrium of urban ecosystems, especially in large metropolitan areas where the pressure of urbanization is intense. However, most existing BHNs fail to account for the dynamic changes and unique requirements of local species, leading to homogenized construction outcomes and ecological corridor objectives. This study employs a comprehensive approach to identify bird habitat patches using multiple high-quality sources, then utilize circuit theory and complex network theory to construct and assess the resilience of BHN. Our key findings showed: (1)93 bird habitat sources were identified, predominantly situated in the continuous green spaces of southern and southeastern Shanghai, whereas habitat sources in the city center and other densely built-up areas are more dispersed, highlighting them as prime targets for future ecological restoration efforts. (2) The distribution of bird habitat corridors exhibits significant spatial heterogeneity, with primary corridors predominantly spanning the southwestern and eastern parts of the study area, while secondary corridors are more abundant in the western and northern parts, forming a denser network, whereas the central area shows fewer and more isolated corridors. (3) The decline in structural and functional resilience was notably more rapid under targeted attacks than under random attacks, underscoring the need to prioritize crucial bird habitat sources on the city's periphery, especially near highly urbanized areas, in urban planning and biodiversity conservation efforts to sustain ecological balance and biodiversity. These insights provide a crucial scientific basis for urban planners, emphasizing the integration of biodiversity conservation into urban development strategies by optimizing ecological sources and corridors to balance development with ecological preservation.
RESUMO
INTRODUCTIN: Improper gait patterns, impaired balance and foot drop consistently plague stroke survivors, preventing them from walking independently and safely. Neuromuscular electrical stimulation (NMES) technology can help patients reactivate their muscles and regain motor coordination. This study aims to systematically review and summarize the evidence for the potential benefits of NMES on the improvement of gait patterns after stroke. EVIDENCE ACQUISITION: PubMed, Cochrane Library, Embase, Science Direct and Web of Science were systematically searched until April 2024, to identify randomized controlled trials with the following criteria: stroke survivors as participants; NMES as intervention; conventional rehabilitation as a comparator; and gait assessment, through scales or quantitative parameters, as outcome measures. EVIDENCE SYNTHESIS: 29 publications involving 1711 patients met the inclusion criteria. Meta-analysis showed no significant differences in Ten-meter walk test, Fugl-Meyer assessment lower extremity, Modified Ashworth Assessment and asymmetry between the NMES group and the control group. Besides, NMES was associated with changes in outcome indicators such as quantitative gait analysis speed [SMD = 0.53, 95% CI (0.20, 0.85), P = 0.001], cadence [SMD = 0.76, 95% CI (0.32, 1.20), P = 0.0008], affected side step length [SMD = 0.73, 95% CI (0.16, 1.31), P = 0.01], angle of ankle dorsiflexion [WMD = 1.57, 95% CI (0.80, 2.33), P < 0.0001], Six-Minute Walk Test [WMD = 14.83, 95% CI (13.55, 16.11), P<0.00001]. According to the PEDro scale, 21 (72.4%) studies were of high quality and 8 were of moderate quality (27.6%). CONCLUSIONS: Taken together, the review synthesis indicated that NMES might play a potential role in stroke-induced walking dysfunction. And NMES may be superior for survivors in the chronic phase than the acute and subacute phases, and the efficacy of short sessions received by patients was greater than that of those who participated in a longer session. Additionally, further comparisons of the effects of NMES with different types or stimulation frequencies may provide unexpected benefits.
Assuntos
Terapia por Estimulação Elétrica , Transtornos Neurológicos da Marcha , Equilíbrio Postural , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Fenômenos Biomecânicos , Terapia por Estimulação Elétrica/métodos , Marcha/fisiologia , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Transtornos Neurológicos da Marcha/reabilitação , Equilíbrio Postural/fisiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia , Reabilitação do Acidente Vascular Cerebral/métodosRESUMO
Rapid synthesis of high-entropy alloy nanoparticles (HEA NPs) offers new opportunities to develop functional materials in widespread applications. Although some methods have successfully produced HEA NPs, these methods generally require rigorous conditions such as high pressure, high temperature, restricted atmosphere, and limited substrates, which impede practical viability. In this work, we report laser solid-phase synthesis of CrMnFeCoNi nanoparticles by laser irradiation of mixed metal precursors on a laser-induced graphene (LIG) support with a 3D porous structure. The CrMnFeCoNi nanoparticles are embraced by several graphene layers, forming graphene shell-encapsulated HEA nanoparticles. The mechanisms of the laser solid-phase synthesis of HEA NPs on LIG supports are investigated through theoretical simulation and experimental observations, in consideration of mixed metal precursor adsorption, thermal decomposition, reduction through electrons from laser-induced thermionic emission, and liquid beads splitting. The production rate reaches up to 30 g/h under the current laser setup. The laser-synthesized graphene shell-encapsulated CrMnFeCoNi NPs loaded on LIG-coated carbon paper are used directly as 3D binder-free integrated electrodes and exhibited excellent electrocatalytic activity towards oxygen evolution reaction with an overpotential of 293 mV at the current density of 10 mA/cm2 and exceptional stability over 428 h in alkaline media, outperforming the commercial RuO2 catalyst and the relevant catalysts reported by other methods. This work also demonstrates the versatility of this technique through the successful synthesis of CrMnFeCoNi oxide, sulfide, and phosphide nanoparticles.
RESUMO
BACKGROUND: Patients may undergo anatomical changes during radiotherapy, leading to an underdosing of the target or overdosing of the organs at risk (OARs). PURPOSE: This study developed a deep-learning method to predict the tumor response of patients with nasopharyngeal carcinoma (NPC) during treatment. This method can predict the anatomical changes of a patient. METHODS: The participants included 230 patients with NPC. The data included planning computed tomography (pCT) and routine cone-beam CT (CBCT) images. The CBCT image quality was improved to the CT level using an advanced method. A long short-term memory network-generative adversarial network (LSTM-GAN) is proposed, which can harness the forecasting ability of LSTM and the generation ability of GAN. Four models were trained to predict the anatomical changes that occurred in weeks 3-6 and named LSTM-GAN-week 3 to LSTM-GAN-week 6. The pCT and CBCT were used as input, and the tumor target volumes (TVs) and OARs were delineated on the predicted and real images (ground truth). Finally, the models were evaluated using contours and dosimetry parameters. RESULTS: The proposed method predicted the anatomical changes, with a dice similarity coefficient above 0.94 and 0.90 for the TVs and surrounding OARs, respectively. The dosimetry parameters were close between the prediction and ground truth. The deviations in the prescription, minimum, and maximum doses of the tumor targets were below 0.5 Gy. For serial organs (brain stem and spinal cord), the deviations in the maximum dose were below 0.6 Gy. For parallel organs (bilateral parotid glands), the deviations in the mean dose were below 0.8 Gy. CONCLUSION: The proposed method can predict the tumor response to radiotherapy in the future such that adaptation can be scheduled on time. This study provides a proactive mechanism for planning adaptation, which can enable personalized treatment and save clinical time by anticipating and preparing for treatment strategy adjustments.
RESUMO
In patients with glioblastoma (GBM), upregulated midkine (MDK) limits the survival benefits conferred by temozolomide (TMZ). RNA interference (RNAi) and CRISPR-Cas9 gene editing technology are attractive approaches for regulating MDK expression. However, delivering these biologics to GBM tissue is challenging. Here we demonstrate a polymer-locking fusogenic liposome (Plofsome) that can be transported across the blood-brain barrier (BBB) and deliver short interfering RNA or CRISPR-Cas9 ribonucleoprotein complexes into the cytoplasm of GBM cells. Plofsome is designed by integrating a 'lock' into the fusogenic liposome using a traceless reactive oxygen species (ROS)-cleavable linker so that fusion occurs only after crossing the BBB and entering the GBM tissue with high ROS levels. Our results showed that MDK suppression by Plofsomes significantly reduced TMZ resistance and inhibited GBM growth in orthotopic brain tumour models. Importantly, Plofsomes are effective only at tumour sites and not in normal tissues, which improves the safety of combined RNAi and CRISPR-Cas9 therapeutics.
RESUMO
This article aims to explore the most optimal pulsed laser energy density when using the pulsed laser deposition (PLD) process to prepare the MoS2 films. We gradually increased the pulsed laser energy density from 70 mJ·cm-2 to 110 mJ·cm-2 and finally determined that 100 mJ·cm-2 was the best-pulsed laser energy density for MoS2 films by PLD. The surface morphology and crystallization of the MoS2 films prepared under this condition are the best. The films consist of a high-crystallized 2H-MoS2 phase with strong (002) preferential orientation, and their direct optical band gap (Eg) is 1.614 eV. At the same time, the Si/MoS2 heterojunction prepared under the optimal pulsed laser energy density shows an opening voltage of 0.61 V and a rectification ratio of 457.0.
RESUMO
This study, aimed at exploring low-maintenance, high-diversity, and sustainable greening strategies for residential areas, conducted a comprehensive survey and analysis of spontaneous plants in residential green spaces in Fuzhou City, documenting 361 species. Employing methods such as variance partitioning, Canonical Correspondence Analysis (CCA), and ecological niche analysis, we investigated the environmental factors influencing the distribution and composition of these plants, as well as their interrelationships. The study found that the composition of spontaneous plants in residential green spaces differs from other urban environments, with a high proportion of alien species (43.77%) due to influences such as resident activities, including a large number of ornamental and edible plants. Maintenance level, urbanization gradient, and green space ratio are common factors affecting the composition and distribution of spontaneous plants in urban environments, while unique residential socio-economic factors like building age, housing prices, and population density significantly affect the spontaneous plants in residential green spaces. The overall dominant plant community shows a significant positive association, indicating a relatively stable stage of succession. Although competition among most species is not significant and interspecific connectivity is weak, the presence of seven dominant invasive species intensifies competition. Based on these findings, the study proposes several specific sustainable management measures: adopting the concept of New Naturalistic Ecological Planting Design, selecting native spontaneous plants with strong adaptability, and constructing plant communities that are ecologically stable and have ornamental value by mimicking natural ecosystems. Additionally, specific methods for managing specific invasive species in residential green spaces using competitive replacement control methods are proposed. These measures aim to promote the health and sustainable development of urban residential green spaces.
Assuntos
Ecossistema , Desenvolvimento Sustentável , China , Conservação dos Recursos Naturais/métodos , Plantas , Urbanização , Cidades , Biodiversidade , Espécies IntroduzidasRESUMO
ABSTRACT: Lipopolysaccharide (LPS) plays an important role in Raw264.7 macrophage ferroptosis and inflammation. Purine-rich element-binding protein B (Purb) influences cellular processes by regulating gene expression as a transcription factor. However, the effect and molecular mechanism of Purb in regulating Raw264.7 macrophage ferroptosis is still unknown. In this study, we used malondialdehyde, glutathione (GSH) assays, Fe 2+ fluorescence, reactive oxygen species staining, and western blotting to determine the effect of Purb on LPS-induced Raw264.7 macrophage ferroptosis. Pharmacological inhibitor of ferroptosis was utilized to explore its potential effects for inflammation by reverse transcription-quantitative polymerase chain reaction analysis. Meanwhile, chromatin immunoprecipitation was performed to verify the binding of Purb and the GSH-dependent peroxidase 4 (Gpx4). The results showed that LPS-induced inflammation in Raw264.7 macrophages was inhibited by ferroptosis inhibitor Fer-1 treatment. LPS inhibited the expression of Purb in Raw264.7 macrophages. In addition, Purb overexpression relieved the ferroptosis, and inflammatory response of Raw264.7 macrophages induced by LPS. Mechanistically, the binding of Purb to the Gpx4 promoter was decreased after LPS stimulation. Therefore, we concluded for the first time that Purb played a critical role in LPS-induced ferroptosis and inflammatory response by regulating the transcription of Gpx4. These results provide a theoretical basis for further research on the macrophage ferroptosis and inflammation.
Assuntos
Ferroptose , Inflamação , Lipopolissacarídeos , Macrófagos , Animais , Ferroptose/efeitos dos fármacos , Camundongos , Lipopolissacarídeos/farmacologia , Células RAW 264.7 , Inflamação/metabolismo , Inflamação/patologia , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: Eradicating Helicobacter pylori infection by bismuth quadruple therapy (BQT) is effective. However, the effect of BQT and subsequent fecal microbiota transplant (FMT) on the gut microbiota is less known. MATERIALS AND METHODS: This prospective randomized controlled trial was conducted at a tertiary hospital in China from January 2019 to October 2020, with the primary endpoints the effect of BQT on the gut microbiota and the effect of FMT on the gut microbiota after bismuth quadruple therapy eradication therapy. A 14-day BQT with amoxicillin and clarithromycin was administered to H. pylori-positive subjects, and after eradication therapy, patients received a one-time FMT or placebo treatment. We then collected stool samples to assess the effects of 14-day BQT and FMT on the gut microbiota. 16 s rDNA and metagenomic sequencing were used to analyze the structure and function of intestinal flora. We also used Gastrointestinal Symptom Rating Scale (GSRS) to evaluate gastrointestinal symptom during treatment. RESULTS: A total of 30 patients were recruited and 15 were assigned to either FMT or placebo groups. After eradication therapy, alpha-diversity was decreased in both groups. At the phylum level, the abundance of Bacteroidetes and Firmicutes decreased, while Proteobacteria increased. At the genus level, the abundance of beneficial bacteria decreased, while pathogenic bacteria increased. Eradication therapy reduced some resistance genes abundance while increased the resistance genes abundance linked to Escherichia coli. While they all returned to baseline by Week 10. Besides, the difference was observed in Week 10 by the diarrhea score between two groups. Compared to Week 2, the GSRS total score and diarrhea score decreased in Week 3 only in FMT group. CONCLUSIONS: The balance of intestinal flora in patients can be considerably impacted by BQT in the short term, but it has reverted back to baseline by Week 10. FMT can alleviate gastrointestinal symptoms even if there was no evidence it promoted restoration of intestinal flora.
Assuntos
Antibacterianos , Bismuto , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/terapia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Transplante de Microbiota Fecal/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Helicobacter pylori/efeitos dos fármacos , Adulto , Antibacterianos/uso terapêutico , Estudos Prospectivos , Bismuto/uso terapêutico , Quimioterapia Combinada , China , Amoxicilina/uso terapêutico , Claritromicina/uso terapêutico , Resultado do Tratamento , Idoso , Fezes/microbiologiaRESUMO
Purpose: Difficulties remain in dose optimization and evaluation of cervical cancer radiotherapy that combines external beam radiotherapy (EBRT) and brachytherapy (BT). This study estimates and improves the accumulated dose distribution of EBRT and BT with deep learning-based dose prediction. Materials and methods: A total of 30 patients treated with combined cervical cancer radiotherapy were enrolled in this study. The dose distributions of EBRT and BT plans were accumulated using commercial deformable image registration. A ResNet-101-based deep learning model was trained to predict pixel-wise dose distributions. To test the role of the predicted accumulated dose in clinic, each EBRT plan was designed using conventional method and then redesigned referencing the predicted accumulated dose distribution. Bladder and rectum dosimetric parameters and normal tissue complication probability (NTCP) values were calculated and compared between the conventional and redesigned accumulated doses. Results: The redesigned accumulated doses showed a decrease in mean values of V50, V60, and D2cc for the bladder (-3.02%, -1.71%, and -1.19 Gy, respectively) and rectum (-4.82%, -1.97%, and -4.13 Gy, respectively). The mean NTCP values for the bladder and rectum were also decreased by 0.02 and 0.98%, respectively. All values had statistically significant differences (p < 0.01), except for the bladder D2cc (p = 0.112). Conclusion: This study realized accumulated dose prediction for combined cervical cancer radiotherapy without knowing the BT dose. The predicted dose served as a reference for EBRT treatment planning, leading to a superior accumulated dose distribution and lower NTCP values.
RESUMO
ε-Poly-L-lysine (ε-PL) is an amino acid homopolymer with diverse potential applications in the food, pharmaceutical and cosmetic industries. To improve its biomanufacturing efficiency, strain engineering and bioprocess optimization were combined in this study. Firstly, a cocktail strain breeding strategy was employed to generate a ε-PL high-production mutant, Streptomyces albulus GS114, with enhanced L-lysine uptake capability. Subsequently, the L-lysine feeding conditions during fed-batch fermentation were systematically optimized to improve the L-lysine supply, resulting in ε-PL production reaching 73.1 ± 1.4 g/L in 5 L bioreactor. Finally, an engineered strain, S. albulus L2, with enhanced uptake capability and polymerization ability of L-lysine was constructed, achieving ε-PL production of 81.4 ± 5.2 g/L by fed-batch fermentation. This represents the highest reported production of ε-PL to date. This study provided an efficient production strategy for ε-PL and valuable insights into the high-value utilization of L-lysine.
Assuntos
Reatores Biológicos , Fermentação , Lisina , Polilisina , Streptomyces , Streptomyces/metabolismo , Polilisina/biossíntese , Lisina/metabolismo , Técnicas de Cultura Celular por LotesRESUMO
Cholesterol homeostasis in neurons is critical for synapse formation and maintenance. Neurons with impaired cholesterol uptake undergo progressive synapse loss and eventual degeneration. To investigate the molecular mechanisms of neuronal cholesterol homeostasis and its role during synapse development, we studied motor neurons of Caenorhabditis elegans because these neurons rely on dietary cholesterol. Combining lipidomic analysis, we discovered that NCR-1, a lysosomal cholesterol transporter, promotes cholesterol absorption and synapse development. Loss of ncr-1 causes smaller synapses, and low cholesterol exacerbates the deficits. Moreover, NCR-1 deficiency hinders the increase in synapses under high cholesterol. Unexpectedly, NCR-2, the NCR-1 homolog, increases the use of cholesterol and sphingomyelins and impedes synapse formation. NCR-2 deficiency causes an increase in synapses regardless of cholesterol concentration. Inhibiting the degradation or synthesis of sphingomyelins can induce or suppress the synaptic phenotypes in ncr-2 mutants. Our findings indicate that neuronal cholesterol homeostasis is differentially controlled by two lysosomal cholesterol transporters and highlight the importance of neuronal cholesterol homeostasis in synapse development.
Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Colesterol , Lisossomos , Animais , Caenorhabditis elegans/metabolismo , Lisossomos/metabolismo , Colesterol/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Junção Neuromuscular/metabolismo , Homeostase , Neurônios Motores/metabolismo , Sinapses/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/genéticaRESUMO
Aims: Despite more and more studies indicate that beverages play an important role in type 2 diabetes mellitus(T2DM), the efficacy of intaking different beverages for T2DM has not been clearly stated in one article. The meta-analysis was performed, which aims to assess the effects of beverages on mortality and cardiovascular complications in patients with type 2 diabetes and the incidence of T2DM. Method: PubMed, Embase, Web of Science and Cochrane Library databases were search up to March, 2023 to identify relevant studies, including studies researching beverage consumption, the incidence and mortality of T2DM and incidence of cardiovascular disease, a kind of complication of T2DM. The way to explore the source of heterogeneity is performing subgroup analyses and sensitivity analyses. Funnel plots and Egger's regression test were performed to assess publication bias. The Hazard ratio (HR) and 95% confidence intervals (95% CIs) were used to analysis the results. Fifteen observational studies were included in our meta-analysis. Results: Fifteen eligible articles were included sugar-sweetened beverages(SSB) consumption increased the mortality and incidence of T2DM ( Hazard ratio (HR), 1.20; 95% confidence interval (CI), 1.05-1.38; P = 0.01 and HR, 1.15; 95% CI,1.06-1.24; P = 0.001), respectively. Artificially-sweetened beverages (ASB) consumption was not associated with the mortality and incidence of T2DM (HR,0.96;95%CI, 0.86-1.07; P = 0.464 and HR, 1.15; 95% CI,1.05-1.26; P = 0.003), respectively. Fruit juice consumption increased the incidence of T2DM (HR,1.08;95%CI,1.02-1.14, P = 0.296).Tea or coffee consumption can reduce the incidence of T2DM (HR, 0.89; 95%CI,0.81-0.98; P = 0.016). Tea or coffee consumption was associated with a lower risk of mortality of T2DM (HR,0.84; 95% Cl, 0.75-0.94; P = 0.002 and HR,0.75; 95% CI, 0.65-0.87; P < 0.001), respectively. Additionally, beverage consumption was not associated with cardiovascular disease in T2DM patients (HR,1.03; 95% Cl, 0.82-1.30, P > 0.05). Conclusions: High consumption of SSBs led to a higher risk and mortality of T2DM, while high consumption of coffee or tea showed significant associations with a lower risk of the incidence and mortality of T2DM. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01396-5.
RESUMO
Nanodevices that function in specific organs or cells are one of the ultimate goals of synthetic biology. The recent progress in DNA nanotechnology such as DNA origami has allowed us to construct nanodevices to deliver a payload (e.g., drug) to the tumor. However, delivery to specific organs remains difficult due to the fragility of the DNA nanostructure and the low targeting capability of the DNA nanostructure. Here, we constructed tough DNA origami that allowed us to encapsulate the DNA origami into lipid-based nanoparticles (LNPs) under harsh conditions (low pH), harnessing organ-specific delivery of the gene of interest (GOI). We found that DNA origami-encapsulated LNPs can increase the functionality of payload GOIs (mRNA and siRNA) inside mouse organs through the contribution from different LNP structures revealed by cryogenic electron microscope (Cryo-EM). These data should be the basis for future organ-specific gene expression control using DNA origami nanodevices.
Assuntos
DNA , Nanotecnologia , DNA/química , Animais , Camundongos , Nanotecnologia/métodos , Nanoestruturas/química , Nanopartículas/química , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , RNA Mensageiro/genética , RNA Mensageiro/química , Regulação da Expressão Gênica , Especificidade de Órgãos , Conformação de Ácido Nucleico , Lipídeos/químicaRESUMO
Patients with heart failure (HF) often experience repeated acute decompensation and develop comorbidities such as chronic kidney disease and frailty syndrome. Although this suggests pathological interaction among comorbidities, the mechanisms linking them are poorly understood. Here, we identified alterations in hematopoietic stem cells (HSCs) as a critical driver of recurrent HF and associated comorbidities. Bone marrow transplantation from HF-experienced mice resulted in spontaneous cardiac dysfunction and fibrosis in recipient mice, as well as increased vulnerability to kidney and skeletal muscle insults. HF enhanced the capacity of HSCs to generate proinflammatory macrophages. In HF mice, global chromatin accessibility analysis and single-cell RNA-seq showed that transforming growth factor-ß (TGF-ß) signaling was suppressed in HSCs, which corresponded with repressed sympathetic nervous activity in bone marrow. Transplantation of bone marrow from mice in which TGF-ß signaling was inhibited similarly exacerbated cardiac dysfunction. Collectively, these results suggest that cardiac stress modulates the epigenome of HSCs, which in turn alters their capacity to generate cardiac macrophage subpopulations. This change in HSCs may be a common driver of repeated HF events and comorbidity by serving as a key carrier of "stress memory."
Assuntos
Insuficiência Cardíaca , Imunidade Inata , Memória Imunológica , Camundongos Endogâmicos C57BL , Animais , Insuficiência Cardíaca/imunologia , Camundongos , Masculino , Multimorbidade , Fator de Crescimento Transformador beta/metabolismo , Células-Tronco Hematopoéticas/imunologia , Transdução de Sinais/imunologia , Macrófagos/imunologia , Imunidade TreinadaRESUMO
BACKGROUND: In this era of rapid technological development, medical schools have had to use modern technology to enhance traditional teaching. Online teaching was preferred by many medical schools. However due to the complexity of intracranial anatomy, it was challenging for the students to study this part online, and the students were likely to be tired of neurosurgery, which is disadvantageous to the development of neurosurgery. Therefore, we developed this database to help students learn better neuroanatomy. MAIN BODY: The data were sourced from Rhoton's Cranial Anatomy and Surgical Approaches and Neurosurgery Tricks of the Trade in this database. Then we designed many hand gesture figures connected with the atlas of anatomy. Our database was divided into three parts: intracranial arteries, intracranial veins, and neurosurgery approaches. Each section below contains an atlas of anatomy, and gestures represent vessels and nerves. Pictures of hand gestures and atlas of anatomy are available to view on GRAVEN ( www.graven.cn ) without restrictions for all teachers and students. We recruited 50 undergraduate students and randomly divided them into two groups: using traditional teaching methods or GRAVEN database combined with above traditional teaching methods. Results revealed a significant improvement in academic performance in using GRAVEN database combined with traditional teaching methods compared to the traditional teaching methods. CONCLUSION: This database was vital to help students learn about intracranial anatomy and neurosurgical approaches. Gesture teaching can effectively simulate the relationship between human organs and tissues through the flexibility of hands and fingers, improving anatomy interest and education.