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1.
Traffic ; 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36412210

RESUMO

AP2S1 is the sigma 2 subunit of adaptor protein 2 (AP2) that is essential for endocytosis. In this study, we investigated the potential role of AP2S1 in intracellular processing of amyloid precursor protein (APP), which contributes to the pathogenesis of Alzheimer's disease (AD) by generating the toxic ß-amyloid peptide (Aß). We found that knockdown or overexpression of AP2S1 decreased or increased the protein levels of APP and Aß in cells stably expressing human full-length APP695, respectively. This effect was unrelated to endocytosis but involved lysosomal degradation. Morphological studies revealed that silencing of AP2S1 promoted the translocalization of APP from RAB9-positive late endosomes (LE) to LAMP1-positive lysosomes, which was paralleled by the enhanced LE-lysosome fusion. In support, silencing of vacuolar protein sorting-associated protein 41 (VPS41) that is implicated in LE-lyso fusion prevented AP2S1-mediated regulation of APP degradation and translocalization. In APP/PS1 mice, an animal model of AD, AAV-mediated delivery of AP2S1 shRNA in the hippocampus significantly reduced the protein levels of APP and Aß, with the concomitant APP translocalization, LE-lyso fusion and the improved cognitive functions. Taken together, these data uncover a LE-lyso fusion mechanism in APP degradation and suggest a novel role for AP2S1 in the pathophysiology of AD.

2.
Front Cell Dev Biol ; 10: 999547, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36393846

RESUMO

Aim: Bladder outlet obstruction (BOO) leads to bladder wall remodeling accompanying the progression from inflammation to fibrosis where pathological hydrostatic pressure (HP)-induced alteration of bladder smooth muscle cells (BSMCs) hypertrophic and excessive extracellular matrix (ECM) deposition play a pivotal role. Recently, we have predicted survivin (BIRC5) as a potential hub gene that might be critical during bladder fibrosis by bioinformatics analyses from rat BOO bladder, but its function during BOO progression remains unknown. Here, we investigated the role of survivin protein on bladder dysfunction of BOO both in vitro and in vivo. Methods: Sprague-Dawley female rats were divided into three groups: control group, BOO group, and BOO followed by the treatment with YM155 group. Bladder morphology and function were evaluated by Masson staining and urodynamic testing. To elucidate the underlying mechanism, hBSMCs were subjected to pathological HP of 200 cm H2O and co-cultured with the presence or absence of survivin siRNA and/or autophagy inhibitor 3-MA. Autophagy was evaluated by the detection of Beclin1 and LC3B-II expression, proliferation was conducted by the EdU analysis and PCNA expression, and fibrosis was assessed by the examination of Col 1 and Fn expression. Results: BOO led to a gradual alteration of hypertrophy and fibrosis of the bladder, and subsequently induced bladder dysfunction accompanied by increased survivin expression, while these histological and function changes were attenuated by the treatment with YM155. HP significantly increased survivin expression, upregulated Col1 and Fn expression, enhanced proliferation, and downregulated autophagy markers, but these changes were partially abolished by survivin siRNA treatment, which was consistent with the results of the BOO rat experiment. In addition, the anti-fibrotic and anti-proliferative effects of the survivin siRNA treatment on hBSMCs were diminished after the inhibition of autophagy by the treatment with 3-MA. Conclusion: In summary, the upregulation of survivin increased cell proliferation and fibrotic protein expression of hBSMC and drove the onset of bladder remodeling through autophagy during BOO. Targeting survivin in pathological hBSMCs could be a promising way to anti-fibrotic therapeutic approach in bladder remodeling secondary to BOO.

3.
Inorg Chem ; 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36399704

RESUMO

The design of electrocatalysts with high activity and the understanding of the reaction mechanism for the ethanol oxidation reaction (EOR) are pivotal for commercializing direct ethanol fuel cells (DEFCs). Herein, island-like nanoporous gold/palladium (INPG/Pd) is designed as a highly efficient EOR electrocatalyst. For a better understanding of the reaction mechanism, in situ surface-enhanced Raman spectroscopy (SERS) in conjunction with H-D isotope replacement is used to investigate the dissociation and oxidation of CH3CH2OH on the INPG/Pd electrode, with a focus on identifying significant intermediate species in the reaction process. The results show that INPG/Pd has a higher electrocatalytic performance than INPG and indium-tin oxide (ITO) glass/palladium (Pd) due to the synergistic effect of NPG and Pd. INPG/Pd-10 shows the highest specific activity, the strongest charge-transfer ability, and relatively good stability. INPG/Pd presents better SERS sensitivity than ITO glass/Pd because of the plasma enhancement effect of nanoporous Au. The in situ Raman spectral results suggest that the oxidation of ethanol proceeds via a dual-pathway (C1 and C2) reaction mechanism. Dehydrogenation of ethanol can form acetaldehyde (CH3CHO) at -0.4 V. Meanwhile, the adsorbed acetaldehyde is oxidized to acetate from approximately -0.4 V, with the potential moving positively, which is the so-called C2 pathway. Alternatively, in the C1 pathway, CH3CHO and CH3CH2OH decomposed to intermediate species (adsorbed CO) on the INPG/Pd electrode due to C-C bond breaking at potentials of approximately -0.2 V. Subsequently, the CO species is oxidized to CO2 at more positive potentials.

4.
Front Oncol ; 12: 1049773, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36408157

RESUMO

Background: In this study, we aimed to investigate the signature of the autophagy-related lncRNAs (ARLs) and perform integrated analysis with immune infiltration in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). Methods and results: The UCSC Xena and HADb databases provided the corresponding data. The ARLs were selected via constructing a co-expression network of autophagy-related genes (ARGs) and lncRNAs. Univariate Cox regression analysis combined with LASSO regression and multivariate Cox regression analysis were utilized to screen lncRNAs. The ARL risk signature was established by Cox regression and tested if it was an independent element bound up with patient prognosis. We used the xCell algorithm and ssGSEA to clarify the pertinence between immune infiltration and the expression of ARLs. Finally, we predicted the sensitivity of drug treatment as well as the immune response. Results indicated that the three prognostic ARLs (SMURF2P1, MIR9-3HG, and AC005332.4) possessed significant diversity and constituted the ARL signature. Risk score was an individual element (HR = 2.82, 95% CI = 1.87-4.30; p < 0.001). Immune infiltration analysis revealed significant increases in central memory CD8+ T cells, endothelial cells, CD8+ naive T cells, and preadipocytes in the high-risk group (p < 0.05). There were 10 therapeutic agents that varied significantly in their estimated half-maximal inhibitory concentrations in the two groups. According to the experimental validation, we found that SMURF2P1 belongs to the co-stimulatory genes and might assume greater importance in the development of cervical adenocarcinoma. MIR9-3HG and AC005332.4 belonged to the tumor-suppressor genes and they may play a more positive role in cervical squamous cell carcinoma. Conclusions: This research explored and validated a novel signature of the ARLs, which can be applied to forecast the prognosis of patients with CESC and is closely associated with immune infiltration.

5.
Front Neurosci ; 16: 1005810, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36408413

RESUMO

Highly precise neuromodulation with a high efficacy poses great importance in neuroscience. Here we developed a candle soot fiber optoacoustic emitter (CSFOE), capable of generating a high pressure of over 10 MPa with a central frequency of 12.8 MHz, enabling highly efficient neuromodulation in vitro. The design of the fiber optoacoustic emitter, including the choice of the material and the thickness of the layered structure, was optimized in both simulations and experiments. The optoacoustic conversion efficiency of the optimized CSFOE was found to be 10 times higher than the other carbon-based fiber optoacoustic emitters. Driven by a single laser, the CSFOE can perform dual-site optoacoustic activation of neurons, confirmed by calcium (Ca2+) imaging. Our work opens potential avenues for more complex and programmed control in neural circuits using a simple design for multisite neuromodulation in vivo.

6.
J Chem Phys ; 157(19): 194114, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36414454

RESUMO

The Jordan-Wigner transformation establishes a duality between su(2) and fermionic algebras. We present qualitative arguments and numerical evidence that when mapping spins to fermions, the transformation makes strong correlation weaker, as demonstrated by the Hartree-Fock approximation to the transformed Hamiltonian. This result can be rationalized in terms of rank reduction of spin shift terms when transformed to fermions. Conversely, the mapping of fermions to qubits makes strong correlation stronger, complicating its solution when one uses qubit-based correlators. The presence of string operators poses challenges to the implementation of quantum chemistry methods on classical computers, but these can be dealt with using established techniques of low computational cost. Our proof of principle results for XXZ and J1-J2 Heisenberg (in 1D and 2D) indicates that the JW transformed fermionic Hamiltonian has reduced complexity in key regions of their phase diagrams and provides a better starting point for addressing challenging spin problems.

7.
Molecules ; 27(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36364318

RESUMO

In this study, a simple colorimetric method was established to detect copper ion (Cu2+), sulfathiazole (ST), and glucose based on the acetylcholinesterase (AChE)-like activity of zeolitic imidazolate framework-8 (ZIF-8). The AChE-like activity of ZIF-8 can hydrolyze acetylthiocholine chloride (ATCh) to thiocholine (TCh), which will further react with 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) to generate 2-nitro-5-thiobenzoic acid (TNB) that has a maximum absorption peak at 405 nm. The effects of different reaction conditions (buffer pH, the volume of ZIF-8, reaction temperature and time, and ATCh concentration) were investigated. Under the optimized conditions, the value of the Michaelis-Menten constant (Km) is measured to be 0.83 mM, which shows a high affinity toward the substrate (ATCh). Meanwhile, the ZIF-8 has good storage stability, which can maintain more than 80.0% of its initial activity after 30 days of storage at room temperature, and the relative standard deviation (RSD) of batch-to-batch (n = 3) is 5.1%. The linear dependences are obtained based on the AChE-like activity of ZIF-8 for the detection of Cu2+, ST, and glucose in the ranges of 0.021-1.34 and 5.38-689.66 µM, 43.10-517.24 µM, and 0.0054-1.40 mM, respectively. The limit of detections (LODs) are calculated to be 20.00 nM, 9.25 µM, and 5.24 µM, respectively. Moreover, the sample spiked recoveries of Cu2+ in lake water, ST in milk, and glucose in strawberry samples were measured, and the results are in the range of 98.4-115.4% with the RSD (n = 3) lower than 3.3%. In addition, the method shows high selectivity in the real sample analysis.


Assuntos
Acetilcolinesterase , Zeolitas , Colorimetria , Acetiltiocolina , Glucose
8.
RSC Adv ; 12(49): 31959-31965, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36380922

RESUMO

Electrorheological (ER) fluid, containing polarized particles within an insulating liquid, represents a smart material, the mechanical properties of which can be altered mainly by an electric field. In this work, ER fluids based on cauliflower iron(ii) oxalate doped titanium particles show excellent rheological and wetting properties by the sample co-precipitation method. The morphology of the particles is observed by SEM and the molecular structure within the particles is obtained via XRD and FTIR. The distribution of elements within the particles is obtained by EDS. Owing to a lower current density than pure iron(ii) oxalate, the SEM and optical images show an obvious chain-like structure within the ER fluids with 2 wt% and 5 wt%, respectively, under 2 kV mm-1. Then, the rheological properties of these ER fluids are tested up to 3 kV mm-1 and the results show a gratifying property of resisting shear with different shear rates (0.1-100 s-1), which is attributed to the appearance of a stable chain-like structure. At the same time, the ER efficiency and the switching performance are obtained and the static yield stress fits the relevant electric field strength well. Ultimately, an excellent sedimentation ratio is obtained from 0 h to 600 h.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36383477

RESUMO

CONTEXT: The influences of diabetes duration and glycemic control and their potential interplays on the risk of heart failure (HF) remain unclear. OBJECTIVE: This work aimed to investigate the association of diabetes duration and glycemic control with the risk of HF. METHODS: A total of 23 754 individuals with diabetes but without HF during the baseline recruitment of UK Biobank were included in this study. Duration of diabetes was self-reported, and the status of glycemic control was reflected by glycated hemoglobin A1c (HbA1c) levels. Their associations with incident HF were assessed using multivariate Cox models adjusting for traditional risk factors. RESULTS: Duration of diabetes and HbA1c levels both were positively associated with the risk of HF. The hazard ratios (HRs) (95% CI) for diabetes durations of 5 to less than 10, 10 to less than 15, and 15 years or more were 1.09 (0.97-1.23), 1.13 (0.97-1.30), and 1.32 (1.15-1.53), respectively (vs < 5 years); and the HRs for HbA1c of 53.0 to less than 58.5 mmol/mol (7.0% to < 7.5%), 58.5 to less than 63.9 mmol/mol (7.5% to < 8.0%), and 63.9 mmol/mol or greater (8.0%) were 1.15 (1.02-1.31), 1.07 (0.91-1.26), and 1.46 (1.30-1.65), respectively (vs < 53.0 mmol/mol [7.0%]). Individuals with the longest disease duration (≥ 15 years) and poorer glycemic control (HbA1c  ≥ 63.9 mmol/mol [8.0%]) had a particularly higher risk of HF (P for interaction = .026). CONCLUSION: The risk of HF among individuals with diabetes increases with a longer duration of diabetes and increasing HbA1c levels. This finding may contribute to the individualized prevention of HF in patients with diabetes if being considered in clinical practices and policy-making.

10.
J Clin Med ; 11(21)2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36362458

RESUMO

OBJECTIVE: Robot-assisted laparoscopic ureteral reimplantation (RALUR) and trans-umbilical multiport laparoscopic ureteral reimplantation (TMLUR) are both minimally invasive procedures for benign distal ureteral stricture (DUS). However, TMLUR has rarely been reported in published research, thus the difference in mid-term outcome of these two procedures warrants investigation. METHODS: Patients who underwent RALUR or TMLUR for pediatric DUS from April 2017 to November 2020 at our institution were retrospectively analyzed and 56 patients were included in this retrospective comparison. Demographic characteristics, perioperative data and follow-up results were collected and analyzed in RALUR and TALUR groups. RESULTS: RALUR and TMLUR were successfully performed in children aged from 12.0 to 142.0 months, without conversion to open ureteral reimplantation. RALUR took shorter operative time than TMLUR (p = 0.005) with less blood loss (p = 0.001). Meanwhile, patients receiving RALUR encountered a greater financial burden (p < 0.001) with less cosmetic satisfaction than TMLUR. The mean mid-term follow-up time for RALUR and TMLUR was 18.29 months and 24.64 months, respectively. Mid-term follow-up data showed that DUS was relieved with improved renal function after surgery in both groups, with no significant difference. CONCLUSIONS: RALUR and TMLUR are both safe and efficient for DUS treatment and achieve comparable mid-term outcomes in children. RALUR can reduce operative time and operative blood loss benefiting from its prominent technical superiority, but may currently bring about greater financial burden, with cosmetic satisfaction remaining to be improved.

11.
J Org Chem ; 87(22): 15703-15712, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36331418

RESUMO

Installing a fluoroalkyl group onto the nitrogen atom of azoles represents a potential strategy for lead optimization in medicinal chemistry. Herein, we describe a method for the N-trifluoropropylation of azoles. This process is accomplished using a combination of regioselective N-vinylation and sequential hydrogenation. The two-step sequence is applicable to a diverse set of azoles and tolerates a wide range of functionalities. In addition, we showcase its practicability and utility through the gram-scale synthesis and the late-stage modification of a complex molecule.


Assuntos
Azóis , Nitrogênio , Azóis/química , Hidrogenação , Catálise
12.
Cancer Lett ; 553: 215995, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36336148

RESUMO

RNA editing is among the most common RNA level modifications for generating amino acid changes. We identified a COPA A-to-I RNA editing event in CRC metastasis. Our results showed that the COPA A-to-I RNA editing rate was significantly increased in metastatic CRC tissues and was closely associated with aggressive tumors in the T and N stages. The COPA I164V protein damaged the Golgi-ER reverse transport function, induced ER stress, promoted the translocation of the transcription factors ATF6, XBP1 and ATF4 into the nucleus, and activated the expression of MALAT1, MET, ZEB1, and lead to CRC cell invasion and metastasis. Moreover, the COPA A-to-I RNA editing rate was positively correlated with the immune infiltration score. Collectively, the COPA I164V protein hijacked ER stress to promote the metastasis of CRC, and the COPA A-to-I RNA editing rate may be a potential predictor for patient response to immune checkpoint inhibitor (ICIs) treatment.

13.
Biosensors (Basel) ; 12(11)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36421167

RESUMO

In this study, the alkaline phosphatase (ALP)-like activity of zeolitic-imidazolate framework-8 (ZIF-8) is reported for the first time. Then, colorimetric sensors for the ascorbic acid oxidase (AAO) and copper ion (Cu2+) detection were developed based on the acetylcholinesterase (AChE)- and ALP-like activities of ZIF-8. The ZIF-8 has good mimetic enzyme activity and exhibits high affinity to the substrates. Its AChE- and ALP-like activities also have good reusability and storage stability. Good linear dependences are obtained in the range of 1.3-250.0 µM (AChE-like activity-based) and 4.5-454.5 µM (ALP-like activity based) for Cu2+ detection. Furthermore, good linear dependence is also obtained based on the ALP-like activity of ZIF-8 for AAO detection in the range of 2.3-454.5 U/L. Their limits of detection (LODs) are calculated to be 0.7 µM, 2.8 µM, and 1.8 U/L, respectively. Finally, the sample spiked recoveries of Cu2+ in tap water, Cu2+, and AAO in human serum and rabbit plasma were measured, and the results are in the range of 80.0-119.3%. In short, the preparation of ZIF-8 is simple, environmentally friendly, and harmless, and can realize highly selective detection of AAO and Cu2+ in an efficient and fast process.

14.
Biomolecules ; 12(11)2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36358907

RESUMO

The insulin family consists of insulin, insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2), their receptors (IR, IGF-1R and IGF-2R), and their binding proteins. All three ligands are involved in cell proliferation, apoptosis, protein synthesis and metabolism due to their homologous sequences and structural similarities. Insulin-like growth factor 2, a member of the insulin family, plays an important role in embryonic development, metabolic disorders, and tumorigenesis by combining with three receptors with different degrees of affinity. The main pathological feature of various fibrotic diseases is the excessive deposition of extracellular matrix (ECM) after tissue and organ damage, which eventually results in organic dysfunction because scar formation replaces tissue parenchyma. As a mitogenic factor, IGF-2 is overexpressed in many fibrotic diseases. It can promote the proliferation of fibroblasts significantly, as well as the production of ECM in a time- and dose-dependent manner. This review aims to describe the expression changes and fibrosis-promoting effects of IGF-2 in the skin, oral cavity, heart, lung, liver, and kidney fibrotic tissues.


Assuntos
Fator de Crescimento Insulin-Like II , Receptor de Insulina , Humanos , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Receptor de Insulina/metabolismo , Fibrose , Matriz Extracelular/metabolismo , Insulina/metabolismo
15.
Micromachines (Basel) ; 13(11)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36363961

RESUMO

The influence of the substrate temperature on the structural, surface morphological, optical and nanomechanical properties of NiO films deposited on glass substrates using radio-frequency magnetron sputtering was examined by X-ray diffraction (XRD), atomic force microscopy (AFM), UV-Visible spectroscopy and nanoindentation, respectively. The results indicate that the substrate temperature exhibits significant influences on both the grain texturing orientation and surface morphology of the films. Namely, the dominant crystallographic orientation of the films switches from (111) to (200) accompanied by progressively roughening of the surface when the substrate temperature is increased from 300 °C to 500 °C. The average transmittance of the NiO films was also found to vary in the range of 60-85% in the visible wavelength region, depending on the substrate temperature and wavelength. In addition, the optical band gap calculated from the Tauc plot showed an increasing trend from 3.18 eV to 3.56 eV with increasing substrate temperature. Both the hardness and Young's modulus of NiO films were obtained by means of the nanoindentation continuous contact stiffness measurements mode. Moreover, the contact angle between the water droplet and film surface also indicated an intimate correlation between the surface energy, hence the wettability, of the film and substrate temperature.

16.
Microb Biotechnol ; 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36353812

RESUMO

Halomonas bluephagenesis TD1.0 was engineered to produce the biofuel propane, bioplastic poly-3-hydroxybutyrate (PHB), and biochemicals mandelate and hydroxymandelate in a single, semi-continuous batch fermentation under non-sterile conditions. Multi-product separation was achieved by segregation of the headspace gas (propane), fermentation broth ([hydroxy]mandelate) and cellular biomass (PHB). Engineering was performed by incorporating the genes encoding fatty acid photodecarboxylase (CvFAP) and hydroxymandelic acid synthase (SyHMAS) into a H. bluephagenesis hmgCAB cassette knockout to channel flux towards (hydroxy)mandelate. Design of Experiment strategies were coupled with fermentation trials to simultaneously optimize each product. Propane and mandelate titres were the highest reported for H. bluephagenesis (62 g/gDCW and 71 ± 10 mg/L respectively) with PHB titres (69% g/gDCW) comparable to other published studies. This proof-of-concept achievement of four easily separated products within one fermentation is a novel achievement probing the versatility of biotechnology, further elevating H. bluephagenesis as a Next Generation Industrial Biotechnology (NGIB) chassis by producing highly valued products at a reduced cost.

17.
Light Sci Appl ; 11(1): 321, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36323662

RESUMO

High precision neuromodulation is a powerful tool to decipher neurocircuits and treat neurological diseases. Current non-invasive neuromodulation methods offer limited precision at the millimeter level. Here, we report optically-generated focused ultrasound (OFUS) for non-invasive brain stimulation with ultrahigh precision. OFUS is generated by a soft optoacoustic pad (SOAP) fabricated through embedding candle soot nanoparticles in a curved polydimethylsiloxane film. SOAP generates a transcranial ultrasound focus at 15 MHz with an ultrahigh lateral resolution of 83 µm, which is two orders of magnitude smaller than that of conventional transcranial-focused ultrasound (tFUS). Here, we show effective OFUS neurostimulation in vitro with a single ultrasound cycle. We demonstrate submillimeter transcranial stimulation of the mouse motor cortex in vivo. An acoustic energy of 0.6 mJ/cm2, four orders of magnitude less than that of tFUS, is sufficient for successful OFUS neurostimulation. OFUS offers new capabilities for neuroscience studies and disease treatments by delivering a focus with ultrahigh precision non-invasively.

18.
Sci Rep ; 12(1): 18664, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333318

RESUMO

Mosquito transmit numbers of parasites and pathogens resulting in fatal diseases. Species identification is a prerequisite for effective mosquito control. Existing morphological and molecular classification methods have evitable disadvantages. Here we introduced Deep learning techniques for mosquito species identification. A balanced, high-definition mosquito dataset with 9900 original images covering 17 species was constructed. After three rounds of screening and adjustment-testing (first round among 3 convolutional neural networks and 3 Transformer models, second round among 3 Swin Transformer variants, and third round between 2 images sizes), we proposed the first Swin Transformer-based mosquito species identification model (Swin MSI) with 99.04% accuracy and 99.16% F1-score. By visualizing the identification process, the morphological keys used in Swin MSI were similar but not the same as those used by humans. Swin MSI realized 100% subspecies-level identification in Culex pipiens Complex and 96.26% accuracy for novel species categorization. It presents a promising approach for mosquito identification and mosquito borne diseases control.


Assuntos
Culex , Mosquitos Vetores , Animais , Humanos , Redes Neurais de Computação
19.
Commun Biol ; 5(1): 1181, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333531

RESUMO

There is increasing evidence suggesting the role of microbiome alterations in relation to pancreatic adenocarcinoma and tumor immune functionality. However, molecular mechanisms of the interplay between microbiome signatures and/or their metabolites in pancreatic tumor immunosurveillance are not well understood. We have identified that a probiotic strain (Lactobacillus casei) derived siderophore (ferrichrome) efficiently reprograms tumor-associated macrophages (TAMs) and increases CD8 + T cell infiltration into tumors that paralleled a marked reduction in tumor burden in a syngeneic mouse model of pancreatic cancer. Interestingly, this altered immune response improved anti-PD-L1 therapy that suggests promise of a novel combination (ferrichrome and immune checkpoint inhibitors) therapy for pancreatic cancer treatment. Mechanistically, ferrichrome induced TAMs polarization via activation of the TLR4 pathway that represses the expression of iron export protein ferroportin (FPN1) in macrophages. This study describes a novel probiotic based molecular mechanism that can effectively induce anti-tumor immunosurveillance and improve immune checkpoint inhibitors therapy response in pancreatic cancer.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Probióticos , Camundongos , Animais , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/metabolismo , Adenocarcinoma/metabolismo , Sideróforos , Microambiente Tumoral , Ferricromo/uso terapêutico , Monitorização Imunológica , Inibidores de Checkpoint Imunológico , Probióticos/farmacologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-36373950

RESUMO

BACKGROUND: The influence of overall air pollution on dementia risk and the potential effect modification by other risk factors remain to be clarified. METHODS: We selected 459,844 UK residents who were free of dementia and had data on the exposure to PM2.5, PM2.5-10, PM10, NO2, and NOx during baseline recruitment. The combined exposure to various PMs and NOx was estimated by using an air pollution score. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incident dementia were estimated by Multivariable Cox models. RESULTS: During a median 11.7 years of follow-up, 5,905 incident cases of all-cause dementia were identified. With the exception of PM2.5-10, all other air pollutants were separately associated with a higher risk of all-cause dementia (all P-trend <0.001) with generally similar associations for dementia subtypes. An increasing air pollution score was associated with higher risks of all-cause as well as individual dementia outcomes, with adjusted HRs (95% CI) of 1.27 (1.18, 1.37) for all-cause dementia, 1.27 (1.14, 1.43) for Alzheimer's disease, and 1.35 (1.16, 1.57) for vascular dementia when comparing the highest with the lowest quartile of the score (all P-trend <0.001). These associations of air pollution score with dementia and its subtypes were observed among never and former smokers but not among current smokers (all P-interaction <0.030). CONCLUSIONS: Air pollution was associated with higher risk of dementia among nonsmokers but not current smokers. Additional studies are required to confirm our findings and to explore the potential mechanisms underlying the possible effect modification by smoking status.

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