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1.
Biomaterials ; 313: 122776, 2025 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39236629

RESUMO

Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management.


Assuntos
Células Dendríticas , Hidrogéis , Melanoma , Cicatrização , Hidrogéis/química , Animais , Células Dendríticas/imunologia , Células Dendríticas/efeitos dos fármacos , Melanoma/terapia , Melanoma/patologia , Cicatrização/efeitos dos fármacos , Humanos , Recidiva Local de Neoplasia/prevenção & controle , Camundongos Endogâmicos C57BL , Anti-Infecciosos/uso terapêutico , Anti-Infecciosos/farmacologia , Camundongos , Linhagem Celular Tumoral , Feminino
3.
PeerJ ; 12: e17776, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39224820

RESUMO

Background: The tcdA gene codes for an important toxin produced by Clostridioides difficile (C. difficile), but there is currently no simple and cost-effective method of detecting it. This article establishes and validates a rapid and visual loop-mediated isothermal amplification (LAMP) assay for the detection of the tcdA gene. Methods: Three sets of primers were designed and optimized to amplify the tcdA gene in C. difficile using a LAMP assay. To evaluate the specificity of the LAMP assay, C. difficile VPI10463 was used as a positive control, while 26 pathogenic bacterial strains lacking the tcdA gene and distilled water were utilized as negative controls. For sensitivity analysis, the LAMP assay was compared to PCR using ten-fold serial dilutions of DNA from C. difficile VPI10463, ranging from 207 ng/µl to 0.000207 pg/µl. The tcdA gene of C.difficile was detected in 164 stool specimens using both LAMP and polymerase chain reaction (PCR). Positive and negative results were distinguished using real-time monitoring of turbidity and chromogenic reaction. Results: At a temperature of 66 °C, the target DNA was successfully amplified with a set of primers designated, and visualized within 60 min. Under the same conditions, the target DNA was not amplified with the tcdA12 primers for 26 pathogenic bacterial strains that do not carry the tcdA gene. The detection limit of LAMP was 20.700 pg/µl, which was 10 times more sensitive than that of conventional PCR. The detection rate of tcdA in 164 stool specimens using the LAMP method was 17% (28/164), significantly higher than the 10% (16/164) detection rate of the PCR method (X2 = 47, p < 0.01). Conclusion: LAMP method is an effective technique for the rapid and visual detection of the tcdA gene of C. difficile, and shows potential advantages over PCR in terms of speed, simplicity, and sensitivity. The tcdA-LAMP assay is particularly suitable for medical diagnostic environments with limited resources and is a promising diagnostic strategy for the screening and detection of C. difficile infection in populations at high risk.


Assuntos
Toxinas Bacterianas , Clostridioides difficile , Infecções por Clostridium , Enterotoxinas , Fezes , Técnicas de Amplificação de Ácido Nucleico , Sensibilidade e Especificidade , Clostridioides difficile/genética , Clostridioides difficile/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico/métodos , Humanos , Toxinas Bacterianas/genética , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/microbiologia , Fezes/microbiologia , Fezes/química , Enterotoxinas/genética , Primers do DNA/genética , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase/métodos , Adulto , Pessoa de Meia-Idade
4.
Front Neurol ; 15: 1432401, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39239395

RESUMO

Background: The systemic immune-inflammation index (SII) is a novel inflammatory marker used to assess the immune-inflammatory status of the human body. The systemic immune inflammation has an interplay and mutual relationship with neurological disorders. Serum neurofilament light chain (sNfL) is widely regarded as a potential biomarker for various neurological diseases. The study aimed to examine the association between SII and sNfL. Methods: This cross-sectional investigation was conducted in a population with complete data on SII and sNfL from the 2013-2014 National Health and Nutrition Examination Survey (NHANES). The SII was calculated by dividing the product of platelet count and neutrophil count by the lymphocyte count. Multivariate linear regression models and smooth curves were used to explore the linear connection between SII and sNfL. Sensitivity analyses, interaction tests, and diabetes subgroup smoothing curve fitting were also performed. Results: A total of 2,025 participants were included in our present research. SII showed a significant positive association with the natural logarithm-transformed sNfL (ln-sNfL) in crude model [0.17 (0.07, 0.28)], partially adjusted model [0.13 (0.03, 0.22)], and fully adjusted model [0.12 (0.02, 0.22)]. In all participants, the positive association between SII and ln-sNfL served as a linear relationship, as indicated by a smooth curve. Interaction tests showed that age, gender, BMI, hypertension, and diabetes did not have a significant impact on this positive association (p for interaction >0.05). The subgroup analysis of diabetes was conducted using smooth curve fitting. It was found that compared to the group without diabetes and the group in a pre-diabetic state, the effect was more pronounced in the group with diabetes. Conclusion: Our findings suggest that there is a positive association between SII and sNfL. Furthermore, in comparison to individuals without diabetes and those in a pre-diabetic state, the positive association between SII and sNfL was more pronounced in individuals with diabetes. Further large-scale prospective studies are needed to confirm the association between SII and sNfL.

5.
PLoS One ; 19(9): e0307516, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39240798

RESUMO

As an important part of terrestrial carbon cycle research, net primary productivity is an important parameter to evaluate the quality of terrestrial ecosystem and plays an important role in the analysis of global climate change and carbon balance. Anhui Province is in the Yangtze River Delta region in eastern China. Based on the theoretical basis of CASA model, this paper uses MODIS NDVI, vegetation type data, meteorological data, and LUCC to estimate the NPP of Anhui Province during 2001-2020 and analyzes its spatial-temporal pattern. The results showed that the average NPP in Anhui province was 508.95 gC· (m2 ·a) -1, and the spatial heterogeneity of NPP was strong, and the high value areas were mainly distributed in the Jiangnan Mountains and Dabie Mountains. NPP increased in most areas of Anhui Province, but decreased significantly in 17.60% of the area, mainly in the central area affected by urban and rural expansion and the transformation of the Yangtze River. The dynamic change of NPP in Anhui province is the result of climate change and land use change. Meteorological data are positively correlated with NPP. Among them, the correlation between temperature and solar radiation is higher, and the correlation between NPP and precipitation is the lowest among the three. The NPP of all land cover types was more affected by temperature than precipitation, especially forest land and grassland. The decrease of cultivated land and the increase of Artificial Surfaces (AS) may have contributed to the decrease of NPP in Anhui Province. Human activities have weakened the increase in NPP caused by climate change. In conclusion, this study refined the drivers of spatial heterogeneity of NPP changes in Anhui province, which is conducive to rational planning of terrestrial ecosystems and carbon balance measures.


Assuntos
Mudança Climática , Ecossistema , China , Ciclo do Carbono , Florestas
6.
J Neuroimmunol ; 396: 578460, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39317078

RESUMO

BACKGROUND: Autoimmune nodopathy (AN) is a very rare new disease entity, especially when combined with membranous nephropathy (MN). METHODS: Antibodies against nodal-paranodal cell adhesion molecules in the serum were detected using cell-based assays. Antibody subtypes against contactin-1 (CNTN1) were confirmed. Cases of anti-CNTN1 antibody-positive AN with and without MN were retrieved through a literature search to compare clinical and electrophysiological characteristics. RESULTS: A 65-year-old male patient with MN developed limb numbness and weakness, along with walking instability. Serum CNTN1 antibodies were positive, primarily those of the IgG4 subtype. Electromyography showed prominent demyelination patterns in both the proximal and distal segments of the nerves compared to the middle nerve trunk. Magnetic resonance imaging revealed enlargement of the bilateral brachial and lumbosacral plexuses and local hyperintensity of the right C5-C6 nerve roots. Thirty-five cases with anti-CNTN1 antibody-positive AN with MN and 51 cases with anti-CNTN1 antibody-positive AN without MN were compared. Furthermore, the proportion of patients with MN combined with AN presenting with acute or subacute onset was higher than that observed in the MN without AN group. Nevertheless, no substantial differences were noted between the two groups concerning the clinical and electrophysiological characteristics, which were mainly elderly men, manifested as sensory ataxia, IgG4 antibody subtype, electrophysiological demyelination, and a certain effect on immunotherapy. CONCLUSION: In cases of electrophysiological manifestation of demyelinating peripheral neuropathy, especially in distal and poximal segments of nerves, AN should be considered, and further screening for renal function should be performed. Concomitant MN does not aggravate or alleviate peripheral nerve symptoms.

7.
Sci Rep ; 14(1): 21922, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39300108

RESUMO

Land use and land cover change (LULCC) have profoundly altered land surface properties and ecosystem functions, including carbon and water production. While mapping these changes from local to global scales has become more achievable due to advancements in earth observations and remote sensing, linking land cover changes to ecosystem functions remains challenging, especially at regional scale. Our study attempts to fill this gap by employing a computationally efficient method and two types of widely used high-resolution satellite images. We first investigated the contribution of landscape composition to ecosystem function by examining how land cover and proportion affected gross primary production (GPP) and evapotranspiration (ET) at six macro-landscapes in Mongolia and Kazakhstan. We hypothesized that both ecosystem and landscape GPP and ET are disproportionate to their composition and, therefore, changes in land cover will have asymmetrical influences on landscape functions. We leveraged a computational-friendly linear downscaling approach to align the coarse spatial resolution of MODIS (500 m) with a fine-grain and localized land cover map developed from Landsat (30 m) for six provinces in countries where intensive LULCC occurred in recent decades. By establishing two metrics-function to composition ratio (F/C) and function to changes in composition change (ΔF/ΔC)-we tested our hypothesis and evaluated the impact of land cover change on ecosystem functions within and among the landscapes. Our results show three major themes. (1) The five land cover types have signature downscaled ET and GPP that appears to vary between the two countries as well as within each country. (2) F/C of ET and GPP of forests is statistically greater than 1 (i.e., over-contributing), whereas F/C of grasslands and croplands is close to or slightly less than 1 (i.e., under-contribution). F/C of barrens is clearly lower than 1 but greater than zero. Specifically, a unit of forest generates 1.085 unit of ET and 1.123 unit of GPP, a unit of grassland generates 0.993 unit of ET and GPP, and a unit of cropland produces 0.987 unit of ET and 0.983 unit of GPP. The divergent F/C values among the land cover classes support the hypothesis that landscape function is disproportionate to its composition. (3) ΔET/ΔC and ΔGPP/ΔC of forests and croplands showed negative values, while grasslands and barrens showed positive values, indicating that converting a unit of forest to other land cover leads to a decrease in ET and GPP, while converting units of grassland or barren to other land cover classes will result in increased ET and GPP. This linear downscaling approach for calculating F/C and ΔF/ΔC is labor-saving and cost-effective for rapid assessment on the impact of land use land cover change on ecosystem functions.

8.
J Environ Manage ; 370: 122585, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39303595

RESUMO

An industrial-scale experiment on dairy manure composting with the control group (Ctrl) and the membrane covering group (CM) was conducted to explore the effects of functional membrane covering on gas emissions, the conversion of carbon and nitrogen, and revealing the underlying mechanisms. Results indicated that CM achieved the synergistic effects on gas mitigation and improved compost product quality. CO2, CH4, N2O, and NH3 emissions were reduced by 81.8%, 87.0%, 82.6%, and 82.2%, respectively. The micro-aerobic condition formed in membrane covering compost pile together with the covering inhibiting effect dominated the mitigation effect. CM significantly downregulated the mcrA gene copies and the value of mcrA/pmoA (p < 0.01), which reduced CH4 emission. CM decreased the nirS and nirK gene copies and increased the nosZ gene copies to reduce N2O emission. Functional Annotation of Prokaryotic Taxa showed that membrane covering effectively amended part of carbon and nitrogen cycles, which stimulated the degradation of organic matter, accelerated compost maturity and reduced the gaseous emissions.

9.
Food Chem ; 463(Pt 2): 141180, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39276541

RESUMO

The effects of chickpea protein (CP) modified by heating and/or high-pressure homogenization (HPH) on the gelling properties of myofibrillar protein under reduced phosphate conditions (5 mM sodium triphosphate, STPP) were investigated. The results showed that heating and HPH dual-modified CP could decrease the cooking loss by 29.57 %, elevate the water holding capacity by 17.08 %, and increase the gel strength by 126.88 %, which conferred myofibrillar protein with gelation performance comparable with, or even surpassing, that of the high-phosphate (10 mM STPP) control. This gelation behavior improvement could be attributed to enhanced myosin tail-tail interactions, decreased myosin thermal stability, elevated trans-gauche-trans disulfide conformation, strengthened hydrophobic interactions and hydrogen bonding, the uncoiling of α-helical structures, the formation of well-networked myofibrillar protein gel, and the disulfide linkages between the myosin heavy chain, actin, and CP subunits. Therefore, the dual-modified CP could be a promising phosphate alternative to develop healthier meat products.

11.
Bioresour Technol ; 412: 131420, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39233181

RESUMO

The effect of different levels of temperature on resistance genes is not clear in mesophilic static composting (<50 °C). This study conducted livestock manure composting with different temperature gradients from 20 to 50 °C, it was found that the reduction rates of risk rank-I antibiotic resistance genes (from 3 % to 66 %), metal resistance genes (from -50 % to 76 %) and bacterial pathogens (from 72 % to 91 %) all increased significantly with increasing temperature from 20 to 50°C. The vulnerability of bacterial communities increased significantly, and the assembly process of bacterial communities changed from deterministic to stochastic with the increase of composting temperature. Higher temperature could accelerate the removal of thermolabile resistance genes hosts or pathogenic hosts carrying mobile genetic elements by directly or indirectly affecting organic acids content. Therefore, for soil safety, the temperature of the manure recycling process should be increased as much as possible.


Assuntos
Bactérias , Compostagem , Resistência Microbiana a Medicamentos , Esterco , Temperatura , Compostagem/métodos , Esterco/microbiologia , Resistência Microbiana a Medicamentos/genética , Bactérias/genética , Bactérias/efeitos dos fármacos , Genes Bacterianos , Microbiologia do Solo , Animais , Farmacorresistência Bacteriana/genética
12.
Theranostics ; 14(15): 5762-5777, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39346535

RESUMO

Rationale: Tunnel nanotube (TNT)-mediated mitochondrial transport is crucial for the development and maintenance of multicellular organisms. Despite numerous studies highlighting the significance of this process in both physiological and pathological contexts, knowledge of the underlying mechanisms is still limited. This research focused on the role of the ROCK inhibitor Y-27632 in modulating TNT formation and mitochondrial transport in retinal pigment epithelial (RPE) cells. Methods: Two types of ARPE19 cells (a retinal pigment epithelial cell line) with distinct mitochondrial fluorescently labeled, were co-cultured and treated with ROCK inhibitor Y-27632. The formation of nanotubes and transport of mitochondria were assessed through cytoskeletal staining and live cell imaging. Mitochondrial dysfunction was induced by light damage to establish a model, while mitochondrial function was evaluated through measurement of oxygen consumption rate. The effects of Y-27632 on cytoskeletal and mitochondrial dynamics were further elucidated through detailed analysis. Results: Y-27632 treatment led to an increase in nanotube formation and enhanced mitochondrial transfer among ARPE19 cells, even following exposure to light-induced damage. Our analysis of cytoskeletal and mitochondrial distribution changes suggests that Y-27632 promotes nanotube-mediated mitochondrial transport by influencing cytoskeletal remodeling and mitochondrial movement. Conclusions: These results suggest that Y-27632 has the ability to enhance mitochondrial transfer via tunneling nanotubes in retinal pigment epithelium, and similarly predict that ROCK inhibitor can fulfill its therapeutic potential through promoting mitochondrial transport in the retinal pigment epithelium in the future.


Assuntos
Amidas , Mitocôndrias , Nanotubos , Piridinas , Epitélio Pigmentado da Retina , Quinases Associadas a rho , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/efeitos dos fármacos , Humanos , Amidas/farmacologia , Piridinas/farmacologia , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Quinases Associadas a rho/metabolismo , Quinases Associadas a rho/antagonistas & inibidores , Linhagem Celular , Citoesqueleto/metabolismo , Citoesqueleto/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Transporte Biológico/efeitos dos fármacos
13.
JACS Au ; 4(9): 3581-3592, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39328752

RESUMO

An electrochemically mediated enzyme process for nicotinamide adenine dinucleotide (NADH) oxidation and biosensing has been developed in which the oxygen-dependent activities of wild-type NADH oxidase are replaced by electrochemical regeneration of the flavin adenine dinucleotide (FAD) cofactor in the active site. Consequently, the present bioelectrocatalysis does not rely on a continuous oxygen supply through bubbling air or pure oxygen in biosynthetic applications, which reduces enzyme stability. The coupled electrochemical and enzymatic catalysis is achieved through a combination of enzyme immobilization on the electrode and electrochemical oxidation of FADH2 in the active site mediated by the electron transfer mediator ferrocene carboxylic acid (FcCA). Furthermore, to minimize the effect of dissolved oxygen when the electrocatalytic process is exposed to air, we successfully designed mutations at the Leu40 and Cys42 sites of Leuconostoc mesenteroides (LmNOx) to block the oxygen passage into the active site and to eliminate the native FAD cofactor regeneration half-reaction. The engineered enzymes, whose activities are significantly reduced or inactive in solution, are electrocatalytically active toward conversion of NADH to NAD+, demonstrating successful FAD cofactor regeneration in the active site via electrochemistry. Finally, we developed two highly responsive electrochemical biosensors for NADH detection which has a superior substrate specific to standard detectors using metal electrodes, and comparable detection range and detection limit (1-3 µM).

14.
Ren Fail ; 46(2): 2407885, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39324542

RESUMO

BACKGROUND: Patients receiving maintenance hemodialysis (MHD) frequently encounter a drop in blood pressure during dialysis, known as intradialytic hypotension (IDH). The AIP is associated with diseases such as diabetes and cardiovascular events. It remains unclear whether the AIP is associated with IDH. The present study aimed to explore the association between AIP and IDH in MHD patients. METHODS: In this multi-center cross-sectional study, we included 1946 adult hemodialysis patients from twenty dialysis centers. Patients were divided into four groups based on the AIP quartiles. Linear regression and multiple logistic regression models were used to analyze the relationship between AIP and IDH. Subgroup analyses were further conducted to assess the robustness of the association between the AIP and IDH. RESULTS: After adjusting for potential confounding variables, each 1-unit increase in AIP was associated with a 21% increase in the odds of IDH. The odds ratios (ORs) of IDH increased gradually with higher quartiles of AIP compared with the Q1 reference group (Q2: OR, 1.41, 95% CI: 0.91-2.18; Q3: OR, 1.63, 95% CI: 1.07-2.49; Q4: OR, 1.57, 95% CI: 1.01-2.42). No interaction was observed in the subgroup analysis stratified by age, sex, history of diabetes, heart failure, and myocardial infarction. CONCLUSION: Elevated AIP levels are associated with a heightened risk of IDH in MHD patients.


Assuntos
Hipotensão , Diálise Renal , Humanos , Estudos Transversais , Feminino , Masculino , Hipotensão/etiologia , Diálise Renal/efeitos adversos , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Falência Renal Crônica/terapia , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Modelos Logísticos , Aterosclerose/etiologia , Aterosclerose/sangue , Adulto , Pressão Sanguínea
15.
J Fungi (Basel) ; 10(9)2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39330401

RESUMO

Based on a multi-locus phylogeny of a combined dataset of ITS, LSU, tef1-α, and rpb2 and comprehensive morphological analyses, we describe three new species from the Melanosporum group of genus Tuber and synonymize T. pseudobrumale and T. melanoexcavatum. Phylogenetically, the three newly described species, T. yunnanense, T. melanoumbilicatum and T. microexcavatum, differ significantly in genetic distance from any previously known species. Morphologically, T. yunnanense is distinctly different from its closest phylogenetically related species, T. longispinosum, due to its long shuttle-shape spores (average the ratio of spore length to spore width for all spores (Qm) = 1.74). Tuber melanoumbilicatum differs from the other species in having a cavity and long shuttle-shaped spores (Qm = 1.65). Although T. microexcavatum sampled ascomata have relatively low maturity, they can be distinguished from its closely related species T. pseudobrumale by the ascomata size, surface warts, and spore number per asci; additionally, phylogenetic analysis supports it as a new species. In addition, molecular analysis from 22 newly collected specimens and Genebank data indicate that T. pseudobrumale and T. melanoexcavatum are clustered into a single well-supported clade (Bootstrap (BS) = 100, posterior probabilities (PP) = 1.0); and morphological characteristics do not differ. Therefore, based on the above evidence and publication dates, we conclude that T. melanoexcavatum is a synonym of T. pseudobrumale. By taking into account current knowledge and combining the molecular, multigene phylogenetic clade arrangement and morphological data, we propose that the Melanosporum group should be divided into four subgroups. Diagnostic morphological features and an identification key of all known species in the Melanosporum group are also included. Finally, we also provide some additions to the knowledge of the characterization of T. pseudobrumale, T. variabilisporum, and T. pseudohimalayense included in subgroup 1 of the Melanosporum group.

16.
Sensors (Basel) ; 24(18)2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39338780

RESUMO

To address the class imbalance issue in network intrusion detection, which degrades performance of intrusion detection models, this paper proposes a novel generative model called VAE-WACGAN to generate minority class samples and balance the dataset. This model extends the Variational Autoencoder Generative Adversarial Network (VAEGAN) by integrating key features from the Auxiliary Classifier Generative Adversarial Network (ACGAN) and the Wasserstein Generative Adversarial Network with Gradient Penalty (WGAN-GP). These enhancements significantly improve both the quality of generated samples and the stability of the training process. By utilizing the VAE-WACGAN model to oversample anomalous data, more realistic synthetic anomalies that closely mirror the actual network traffic distribution can be generated. This approach effectively balances the network traffic dataset and enhances the overall performance of the intrusion detection model. Experimental validation was conducted using two widely utilized intrusion detection datasets, UNSW-NB15 and CIC-IDS2017. The results demonstrate that the VAE-WACGAN method effectively enhances the performance metrics of the intrusion detection model. Furthermore, the VAE-WACGAN-based intrusion detection approach surpasses several other advanced methods, underscoring its effectiveness in tackling network security challenges.

17.
Bioorg Chem ; 153: 107842, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39342890

RESUMO

c-MYC is a proto-oncogene ubiquitously overexpressed in various cancers. The formation of G-quadruplex (G4) structures within the c-MYC promoter region can regulate its transcription by interfering with protein binding. Consequently, small molecules targeting c-MYC G4 have emerged as promising anticancer agents. Herein, we report that sanguinarine (SG) and its analogs exhibit a high affinity for c-MYC G4 and potently modulate G4-protein interactions within a natural product library. Notably, SG uniquely enhances NM23-H2 binding to c-MYC G4, both in vitro and in cellular contexts, leading to c-MYC transcriptional repression and subsequent inhibition of cancer cell growth in an NM23-H2-dependent manner. Mechanistic studies and molecular modeling suggest that SG binds to the c-MYC G4/NM23-H2 interface, acting as an orthosteric stabilizer of the DNA-protein complex and preventing c-MYC transcription. Our findings identify SG as a potent c-MYC transcription inhibitor and provide a novel strategy for developing G4-targeting anticancer therapeutics through modulation of G4-protein interactions.

18.
Huan Jing Ke Xue ; 45(9): 5106-5116, 2024 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-39323129

RESUMO

In Shijiazhuang City, ozone (O3) pollution occurs frequently in June every year. In June 2023, the average O3 8 h concentration (O3-8h) pollution exceeded 80% of the days in the month, and O3 was the primary pollutant, accounting for 100%. For an O3 heavy pollution process from June 11 to 18, the air quality model WRF-CMAQ was used for simulation, and the average error data MFB and MFE were -10.47% and 17.96%, respectively, which was within the ideal error range. The CMAQ process analysis module was used to simulate the physical and chemical processes in Shijiazhuang City, and the dry deposition (DDEP) contribution concentration was -23.88 µg·m-3, which was the main process of O3 consumption, whereas the transport process (TRAN) was the main source of O3, among which the contribution was more significant in vertical transport (VTRA). At the same time, the source analysis module (ISAM) was used to analyze the O3 contribution of local and surrounding areas in Shijiazhuang City. The results showed that the contribution rate of local industry sources in Shijiazhuang City was as follows: traffic source (12.54%) > industrial source (6.94%) > residential source (6.56%) > power source (4.75%). The long-distance transmission source (BCON) continued to be in the first place with a high contribution rate of 63.31%. In the heavy pollution period under stable weather, the contribution concentration of BCON in the D02 layer of the nested domain to Shijiazhuang City was lower than the sum of the marked area. Among the surrounding cities, Baoding City had the highest contribution rate under stable weather, accounting for 26.21%. In the late period, the contribution concentration of Xingtai City increased rapidly under the action of high-value southwest wind. To effectively reduce O3 pollution, it is necessary to reduce emissions in the city and to control the upwind cities in advance, and the implementation of inter-regional joint prevention and control is the key.

19.
Sci Total Environ ; 954: 176238, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39277006

RESUMO

Vermicomposting is an efficient bioconversion technology for recycling nutrients from organic waste materials. The biodegradability of raw materials has a significant impact on the earthworm transformation product. However, the management of carbon bioavailability is often overlooked during the vermicomposting process due to the varying degradability of C-rich source in different organic waste. This research aims to investigate the impact of different bioavailable carbon compositions on vermicomposting and to develop a strategy for efficient carbon management. The study involved systematic vermicomposting using four different biodegradable carbon sources (pineapple peels, rice straw, tomato straw, and sawdust) with varying carbon­nitrogen ratios (ranging from 24 to 42). The earthworm production and vermicompost quality were comprehensively evaluated, along with the influence of carbon components on microbial community structure. The results indicated that the optimal vermicomposting treatments were achieved at PCM24, RCM30, TCM30, and MCM30 treatments. Maintaining an approximate ratio of 1:(0.5-1.3) between available and recalcitrant carbon components based on the optimal carbon­nitrogen ratio was found to be optimal for regulating vermicomposting products. Increasing the proportion of available carbon enhanced the quality of vermicompost fertilizer, while a higher proportion of recalcitrant carbon could improve earthworm biomass production efficiency. Labile carbon proportion I (LCP1) and available carbon component (ACC) were identified as key indicators in influencing the formation of microbial community structure. Different carbon compositions led to the specific development and formation of microbial communities, further resulting in significant variations in vermicompost quality under the mediation of microbes. This study, for the first time, clarifies the impact of vermicomposting performance and microbial community from the perspective of carbon bioavailability, which is of great significance for the oriented regulation the vermicomposting efficiency and product in practice.

20.
Front Cell Infect Microbiol ; 14: 1423541, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39233907

RESUMO

Background: Patients who were infected by the Human Immunodeficiency Virus (HIV) could have weakened immunity that is complicated by opportunistic infections, especially for Mycobacterium tuberculosis (MTB). Notably, the HIV-MTB co-infection will accelerate the course of disease progress and greatly increase the mortality of patients. Since the traditional diagnostic methods are time-consuming and have low sensitivity, we aim to investigate the performance of mNGS (metagenomic Next-Generation Sequencing) and mNPS (metagenomic NanoPore Sequencing) for the rapid diagnosis of tuberculosis in HIV-infected patients. Methods: The 122 HIV-infected patients were enrolled for the retrospective analysis. All of the patients underwent traditional microbiological tests, mNGS, and (or) mNPS tests. The clinical comprehensive diagnosis was used as the reference standard to compare the diagnostic performance of culture, mNGS, and mNPS on tuberculosis. We also investigate the diagnostic value of mNGS and mNPS on mixed-infection. Furthermore, the treatment adjustment directed by mNGS and mNPS was analyzed. Results: Compared with the composite reference standard, the culture showed 42.6% clinical sensitivity and 100% specificity, and the OMT(other microbiological testing) had 38.9% sensitivity and 100% specificity. The mNGS had 58.6% clinical sensitivity and 96.8% specificity, and the mNPS had 68.0% clinical sensitivity and 100% specificity. The proportion of mixed-infection cases (88.9%) in the TB group was higher than those in the non-TB group (54.8%) and the mNGS and mNPS are more competitive on mixed-infection diagnosis compared with the traditional methods. Furthermore, there are 63 patients (69.2%) and 36 patients (63.2%) achieved effective treatment after receiving the detection of mNPS and mNGS, respectively. Conclusion: Our study indicated that mNPS and mNGS have high sensitivity and specificity for TB diagnosis compared with the traditional methods, and mNPS seems to have better diagnostic performance than mNGS. Moreover, mNGS and mNPS showed apparent advantages in detecting mixed infection. The mNPS and mNGS-directed medication adjustment have effective treatment outcomes for HIV-infected patients who have lower immunity.


Assuntos
Coinfecção , Infecções por HIV , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Mycobacterium tuberculosis , Sequenciamento por Nanoporos , Sensibilidade e Especificidade , Tuberculose , Humanos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Masculino , Tuberculose/diagnóstico , Tuberculose/microbiologia , Feminino , Infecções por HIV/complicações , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Coinfecção/diagnóstico , Coinfecção/microbiologia , Coinfecção/virologia , Sequenciamento por Nanoporos/métodos , Metagenômica/métodos
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