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1.
Cell ; 186(6): 1279-1294.e19, 2023 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-36868220

RESUMO

Antarctic krill (Euphausia superba) is Earth's most abundant wild animal, and its enormous biomass is vital to the Southern Ocean ecosystem. Here, we report a 48.01-Gb chromosome-level Antarctic krill genome, whose large genome size appears to have resulted from inter-genic transposable element expansions. Our assembly reveals the molecular architecture of the Antarctic krill circadian clock and uncovers expanded gene families associated with molting and energy metabolism, providing insights into adaptations to the cold and highly seasonal Antarctic environment. Population-level genome re-sequencing from four geographical sites around the Antarctic continent reveals no clear population structure but highlights natural selection associated with environmental variables. An apparent drastic reduction in krill population size 10 mya and a subsequent rebound 100 thousand years ago coincides with climate change events. Our findings uncover the genomic basis of Antarctic krill adaptations to the Southern Ocean and provide valuable resources for future Antarctic research.


Assuntos
Euphausiacea , Genoma , Animais , Relógios Circadianos/genética , Ecossistema , Euphausiacea/genética , Euphausiacea/fisiologia , Genômica , Análise de Sequência de DNA , Elementos de DNA Transponíveis , Evolução Biológica , Adaptação Fisiológica
2.
Gastroenterology ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38583724

RESUMO

BACKGROUND & AIMS: Benign ulcerative colorectal diseases (UCDs) such as ulcerative colitis, Crohn's disease, ischemic colitis, and intestinal tuberculosis share similar phenotypes with different etiologies and treatment strategies. To accurately diagnose closely related diseases like UCDs, we hypothesize that contextual learning is critical in enhancing the ability of the artificial intelligence models to differentiate the subtle differences in lesions amidst the vastly divergent spatial contexts. METHODS: White-light colonoscopy datasets of patients with confirmed UCDs and healthy controls were retrospectively collected. We developed a Multiclass Contextual Classification (MCC) model that can differentiate among the mentioned UCDs and healthy controls by incorporating the tissue object contexts surrounding the individual lesion region in a scene and spatial information from other endoscopic frames (video-level) into a unified framework. Internal and external datasets were used to validate the model's performance. RESULTS: Training datasets included 762 patients, and the internal and external testing cohorts included 257 patients and 293 patients, respectively. Our MCC model provided a rapid reference diagnosis on internal test sets with a high averaged area under the receiver operating characteristic curve (image-level: 0.950 and video-level: 0.973) and balanced accuracy (image-level: 76.1% and video-level: 80.8%), which was superior to junior endoscopists (accuracy: 71.8%, P < .0001) and similar to experts (accuracy: 79.7%, P = .732). The MCC model achieved an area under the receiver operating characteristic curve of 0.988 and balanced accuracy of 85.8% using external testing datasets. CONCLUSIONS: These results enable this model to fit in the routine endoscopic workflow, and the contextual framework to be adopted for diagnosing other closely related diseases.

3.
Brief Bioinform ; 24(5)2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37615358

RESUMO

Non-coding RNA (ncRNA) plays a critical role in biology. ncRNAs from the same family usually have similar functions, as a result, it is essential to predict ncRNA families before identifying their functions. There are two primary methods for predicting ncRNA families, namely, traditional biological methods and computational methods. In traditional biological methods, a lot of manpower and resources are required to predict ncRNA families. Therefore, this paper proposed a new ncRNA family prediction method called MFPred based on computational methods. MFPred identified ncRNA families by extracting sequence features of ncRNAs, and it possessed three primary modules, including (1) four ncRNA sequences encoding and feature extraction module, which encoded ncRNA sequences and extracted four different features of ncRNA sequences, (2) dynamic Bi_GRU and feature fusion module, which extracted contextual information features of the ncRNA sequence and (3) ResNet_SE module that extracted local information features of the ncRNA sequence. In this study, MFPred was compared with the previously proposed ncRNA family prediction methods using two frequently used public ncRNA datasets, NCY and nRC. The results showed that MFPred outperformed other prediction methods in the two datasets.


Assuntos
Biologia Computacional , RNA não Traduzido , Humanos , Biologia Computacional/métodos , RNA não Traduzido/genética
4.
J Am Chem Soc ; 146(12): 8372-8380, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38499472

RESUMO

Here we present a highly enantioselective [2π + 2σ] photocycloaddition of bicyclo[1.1.0]butanes (BCBs). The reaction uses a variety of vinylazaarenes as partners and is catalyzed by a polycyclic aromatic hydrocarbon (PAH)-containing chiral phosphoric acid as a bifunctional chiral photosensitizer. A wide array of pharmaceutically important bicyclo[2.1.1]hexane (BCH) derivatives have been synthesized with high yields, enantioselectivity, and diastereoselectivity. In addition to the diverse 1-ketocarbonyl-3-substituted BCBs, α/ß-substituted vinylazaarenes are compatible with such an unprecedented photoredox catalytic pathway, resulting in the successful assembly of an all-carbon quaternary stereocenter or two adjacent tertiary stereocenters on the product.

5.
Int J Cancer ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733360

RESUMO

Low-grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high-risk human papillomavirus (HR-HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community-based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed-up at 6, 12, and 24 months, post-diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1-hydroxipayrene (1-OHP) level. Our results showed that the 1-OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P < .05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24-2.67), (1.98, 1.42-2.75), and (2.37, 1.61-3.49) at 6, 12, and 24 months, post-diagnosis, respectively. The effect was enhanced with HR-HPV positivity, as determined at 6 (1.82, 1.24-2.67), 12 (3.02, 1.74-5.23), and 24 (2.51, 1.48-4.26) months, post-diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR-HPV-positive patients than in HR-HPV-negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR-HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia.

6.
Cancer Immunol Immunother ; 73(5): 95, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607586

RESUMO

BACKGROUND: Homologous recombination deficiency (HRD), though largely uncharacterized in clear cell renal cell carcinoma (ccRCC), was found associated with RAD51 loss of expression. PBRM1 is the second most common mutated genes in ccRCC. Here, we introduce a HRD function-based PBRM1-RAD51 ccRCC classification endowed with diverse immune checkpoint blockade (ICB) responses. METHODS: Totally 1542 patients from four independent cohorts were enrolled, including our localized Zhongshan hospital (ZSHS) cohort and Zhongshan hospital metastatic RCC (ZSHS-mRCC) cohort, The Cancer Genome Atlas (TCGA) cohort and CheckMate cohort. The genomic profile and immune microenvironment were depicted by genomic, transcriptome data and immunohistochemistry. RESULTS: We observed that PBRM1-loss ccRCC harbored enriched HRD-associated mutational signature 3 and loss of RAD51. Dual-loss of PBRM1 and RAD51 identified patients hyper-sensitive to immunotherapy. This dual-loss subtype was featured by M1 macrophage infiltration. Dual-loss was, albeit homologous recombination defective, with high chromosomal stability. CONCLUSIONS: PBRM1 and RAD51 dual-loss ccRCC indicates superior responses to immunotherapy. Dual-loss ccRCC harbors an immune-desert microenvironment but enriched with M1 macrophages. Dual-loss ccRCC is susceptible to defective homologous recombination but possesses high chromosomal stability.


Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/terapia , Imunoterapia , Neoplasias Renais/genética , Neoplasias Renais/terapia , Instabilidade Cromossômica , Microambiente Tumoral , Rad51 Recombinase , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/genética
7.
Small ; 20(7): e2303506, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37806770

RESUMO

Aseptic loosening of prostheses is a highly researched topic, and wear particle-induced macrophage polarization is a significant cause of peri-prosthetic osteolysis. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs-Exos) promote M2 polarization and inhibit M1 polarization of macrophages. However, clinical application problems such as easy clearance and lack of targeting exist. Exosomes derived from M2 macrophages (M2-Exos) have good biocompatibility, immune escape ability, and natural inflammatory targeting ability. M2-Exos and BMSCs-Exos fused exosomes (M2-BMSCs-Exos) are constructed, which targeted the osteolysis site and exerted the therapeutic effect of both exosomes. M2-BMSCs-Exos achieved targeted osteolysis after intravenous administration inhibiting M1 polarization and promoting M2 polarization to a greater extent at the targeted site, ultimately playing a key role in the prevention and treatment of aseptic loosening of prostheses. In conclusion, M2-BMSCs-Exos can be used as a precise and reliable molecular drug for peri-prosthetic osteolysis. Fused exosomes M2-BMSCs-Exos  were originally proposed and successfully prepared, and exosome fusion technology provides a new theoretical basis and solution for the clinical application of therapeutic exosomes.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Osteólise , Humanos , Administração Intravenosa , Macrófagos
8.
Toxicol Appl Pharmacol ; 484: 116859, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38342443

RESUMO

When liver or intestinal function is impaired, bilirubin accumulates in the body and leads to neonatal jaundice. However, the potential negative effects caused by excessive accumulation of bilirubin such as developmental immunotoxicity and neurotoxicity remain unclear. We used a zebrafish model to establish bilirubin-induced jaundice symptoms and evaluated the toxic effects of bilirubin in aquatic organisms. Firstly, our results suggested that bilirubin exposure markedly decreased the survival rate, induced the developmental toxicity and increased the yellow pigment deposited in the zebrafish tail. Meanwhile, the number of macrophages and neutrophils was substantially reduced in a concentration-dependent manner. Besides, the antioxidant enzyme activities were greatly elevated while the inflammatory genes were significantly decreased after bilirubin exposure. Secondly, transcriptome analysis identified 708 genes were differentially expressed after bilirubin exposure, which animal organ morphogenesis, chemical synaptic transmission, and MAPK / mTOR signaling pathways were significantly enriched. Thirdly, bilirubin exposure leads to a significant decrease in the motility of zebrafish, including a dose-dependent decrease in the travelled distance, movement time, and average velocity. Moreover, the innate immune genes and apoptosis-related genes such as TLR4, NF-κB p65, STAT3 and p53 were elevated at a concentration of 10 µg/mL of bilirubin. Finally, our results further revealed that the anti-inflammatory and neuroprotective minocycline could partially rescue the bilirubin-induced neurobehavioral disorders in zebrafish embryos. In conclusion, our study explored the bilirubin-induced immunotoxicity and neurotoxicity in aquatic organisms, which will provide a theoretical basis for the treatment of neonatal jaundice in clinical practice.


Assuntos
Icterícia Neonatal , Poluentes Químicos da Água , Animais , Peixe-Zebra/metabolismo , Minociclina/farmacologia , Bilirrubina , Icterícia Neonatal/metabolismo , Imunidade Inata , Estresse Oxidativo , Antioxidantes/farmacologia , Embrião não Mamífero , Poluentes Químicos da Água/toxicidade
9.
BMC Cancer ; 24(1): 64, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216964

RESUMO

BACKGROUND: Cancer associated fibroblasts (CAFs) can remodel tumor microenvironment by secreting exosomes. This study aimed to investigate the role of exosomes derived from cancer-associated fibroblasts in colorectal cancer (CRC) progression. METHODS: Circular RNA (circRNA) array was used to identify differentially expressed circRNAs in exosomes from normal fibroblasts (NFs) and CAFs, and confirmed one differentially expressed circRNA circ_0067557 by real-time PCR. The effect of circ_0067557 on proliferation, metastasis, chemoresistance and apoptosis was verified by wound heal, tranwell, CCK8, sphere-forming and flow cytometry assay. RESULTS: Circ_0067557 expression in exosomes from CAFs was higher than those from NFs. CAF-derived exosomes promoted the proliferation, migration, invasion and chemoresistance of CRC cells while suppressed apoptosis. Silencing of circ_0067557 inhibited malignant phenotypes of CRC cells by targeting Lin28A and Lin28B. Moreover, CAF-derived exosomes enhanced the growth of CRC xenograft tumors. CONCLUSION: Circ_0067557/Lin28A and Lin28B signal axis may be a potential therapy target for CRC.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Colorretais , Exossomos , MicroRNAs , Humanos , Fibroblastos Associados a Câncer/metabolismo , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Transformação Celular Neoplásica/metabolismo , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Exossomos/genética , Exossomos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Microambiente Tumoral/genética , Animais
10.
Mol Psychiatry ; 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37468529

RESUMO

Deep brain regions such as hippocampus, insula, and amygdala are involved in neuropsychiatric disorders, including chronic insomnia and depression. Our recent reports showed that transcranial alternating current stimulation (tACS) with a current of 15 mA and a frequency of 77.5 Hz, delivered through a montage of the forehead and both mastoids was safe and effective in intervening chronic insomnia and depression over 8 weeks. However, there is no physical evidence to support whether a large alternating current of 15 mA in tACS can send electrical currents to deep brain tissue in awake humans. Here, we directly recorded local field potentials (LFPs) in the hippocampus, insula and amygdala at different current strengths (1 to 15 mA) in 11 adult patients with drug-resistant epilepsy implanted with stereoelectroencephalography (SEEG) electrodes who received tACS at 77.5 Hz from 1 mA to 15 mA at 77.5 Hz for five minutes at each current for a total of 40 min. For the current of 15 mA at 77.5 Hz, additional 55 min were applied to add up a total of 60 min. Linear regression analysis revealed that the average LFPs for the remaining contacts on both sides of the hippocampus, insula, and amygdala of each patient were statistically associated with the given currents in each patient (p < 0.05-0.01), except for the left insula of one subject (p = 0.053). Alternating currents greater than 7 mA were required to produce significant differences in LFPs in the three brain regions compared to LFPs at 0 mA (p < 0.05). The differences remained significant after adjusting for multiple comparisons (p < 0.05). Our study provides direct evidence that the specific tACS procedures are capable of delivering electrical currents to deep brain tissues, opening a realistic avenue for modulating or treating neuropsychiatric disorders associated with hippocampus, insula, and amygdala.

11.
Pharmacol Res ; 204: 107209, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38740147

RESUMO

Considerable progress has recently been made in cancer immunotherapy, including immune checkpoint blockade, cancer vaccine, and adoptive T cell methods. The lack of effective targets is a major cause of the low immunotherapy response rate in colorectal cancer (CRC). Here, we used a proteogenomic strategy comprising immunopeptidomics, whole exome sequencing, and 16 S ribosomal DNA sequencing analyses of 8 patients with CRC to identify neoantigens and bacterial peptides that can serve as antitumor targets. This study directly identified several personalized neoantigens and bacterial immunopeptides. Immunoassays showed that all neoantigens and 5 of 8 bacterial immunopeptides could be recognized by autologous T cells. Additionally, T cell receptor (TCR) αß sequencing revealed the TCR repertoire of epitope-reactive CD8+ T cells. Functional studies showed that T cell receptor-T (TCR-T) could be activated by epitope pulsed lymphoblastoid cells. Overall, this study comprehensively profiled the CRC immunopeptidome, revealing several neoantigens and bacterial peptides with potential to serve as immunotherapy targets in CRC.


Assuntos
Antígenos de Neoplasias , Neoplasias Colorretais , Imunoterapia , Proteogenômica , Humanos , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/terapia , Neoplasias Colorretais/genética , Proteogenômica/métodos , Imunoterapia/métodos , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/genética , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Peptídeos/imunologia , Linfócitos T CD8-Positivos/imunologia
12.
Diabetes Obes Metab ; 26(1): 135-147, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37779362

RESUMO

AIM: Genome-wide association studies (GWAS) have identified multiple susceptibility loci associated with insulin resistance (IR)-relevant phenotypes. However, the genes responsible for these associations remain largely unknown. We aim to identify susceptibility genes for IR-relevant phenotypes via a transcriptome-wide association study. MATERIALS AND METHODS: We conducted a large-scale multi-tissue transcriptome-wide association study for IR (Insulin Sensitivity Index, homeostasis model assessment-IR, fasting insulin) and lipid-relevant traits (high-density lipoprotein cholesterol, triglycerides, low-density lipoprotein cholesterol and total cholesterol) using the largest GWAS summary statistics and precomputed gene expression weights of 49 human tissues. Conditional and joint analyses were implemented to identify significantly independent genes. Furthermore, we estimated the causal effects of independent genes by Mendelian randomization causal inference analysis. RESULTS: We identified 1190 susceptibility genes causally associated with IR-relevant phenotypes, including 58 genes that were not implicated in the original GWAS. Among them, 11 genes were further supported in differential expression analyses or a gene knockout mice database, such as KRIT1 showed both significantly differential expression and IR-related phenotypic effects in knockout mice. Meanwhile, seven proteins encoded by susceptibility genes were targeted by clinically approved drugs, and three of these genes (H6PD, CACNB2 and DRD2) have been served as drug targets for IR-related diseases/traits. Moreover, drug repurposing analysis identified four compounds with profiles opposing the expression of genes associated with IR risk. CONCLUSIONS: Our study provided new insights into IR aetiology and avenues for therapeutic development.


Assuntos
Resistência à Insulina , Transcriptoma , Animais , Humanos , Camundongos , LDL-Colesterol , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Resistência à Insulina/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Análise da Randomização Mendeliana
13.
J Immunol ; 208(1): 181-189, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34880108

RESUMO

The 0.8-Mb Ig new Ag receptor (IgNAR) region of the whitespotted bamboo shark (Chiloscyllium plagiosum) is incompletely assembled in Chr_44 of the reference genome. Here we used Cas9-assisted targeting of chromosome segments (CATCH) to enrich the 2 Mb region of the Chr_44 IgNAR loci and sequenced it by PacBio and next-generation sequencing. A fragment >3.13 Mb was isolated intact from the RBCs of sharks. The target was enriched 245.531-fold, and sequences had up to 94% coverage with a 255× mean depth. Compared with the previously published sequences, 20 holes were filled, with a total length of 3508 bp. In addition, we report five potential germline V alleles of IgNAR1 from six sharks that may belong to two clusters of the IgNAR. Our results provide a new method to research the germline of large Ig gene segments, as well as provide the enhanced bamboo shark IgNAR gene loci with fewer gaps.


Assuntos
Proteínas de Peixes/genética , Loci Gênicos/genética , Imunoglobulinas/genética , Receptores de Antígenos/genética , Tubarões/imunologia , Animais , Proteína 9 Associada à CRISPR , Sistemas CRISPR-Cas , Genoma , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Análise de Sequência de DNA
14.
J Fluoresc ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771406

RESUMO

The tip of a piece of plastic fiber was dyed with thymol blue to form a temperature probe. The fiber optic sensor was calibrated on a heatboard by comparison with a K-type thermal couple. Fluorescence characteristics including fluorescence intensity, emission bandwidth, peak & barycenter wavelengths, and self-referenced intensity ratio were used to carry the information of environment temperature. Accordingly, more than five temperature sensing functions were retrieved from the fluorescent sensor. Among such functions, the emission band barycenter showed premium precision. Temperature-driven shift of the emission band barycenter has a sensitivity of 0.095 nm/K, with a nonlinearity of 2.2%FS, resolution of 4 K and repeatability of 1.8%FS. The sensor can find its applications in wearable devices and radiofrequency ablation. Finally in a verification experiment, the sensor was used to monitor the temperature of a microwave oven chamber in real time.

15.
J Nanobiotechnology ; 22(1): 152, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575979

RESUMO

Infected wound healing remains a challenging task in clinical practice due to several factors: (I) drug-resistant infections caused by various pathogens, (II) persistent inflammation that hinders tissue regeneration and (III) the ability of pathogens to persist intracellularly and evade antibiotic treatment. Microneedle patches (MNs), recognized for their effecacious and painless subcutaneous drug delivery, could greatly enhance wound healing if integrated with antibacterial functionality and tissue regenerative potential. A multifunctional agent with subcellular targeting capability and contained novel antibacterial components, upon loading onto MNs, could yield excellent therapeutic effects on wound infections. In this study, we sythesised a zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) loaded with low molecular weight fucoidan (Fu) and further coating by hyaluronic acid (HA), obtained a multifunctional HAZ@Fu NPs, which could hinders Methicillin-resistant Staphylococcus aureus (MRSA) growth and promotes M2 polarization in macrophages. We mixed HAZ@Fu NPs with photocrosslinked gelatin methacryloyl (GelMA) and loaded it into the tips of the MNs (HAZ@Fu MNs), administered to mice model with MRSA-infected full-thickness cutaneous wounds. MNs are able to penetrate the skin barrier, delivering HAZ@Fu NPs into the dermal layer. Since cells within infected tissues extensively express the HA receptor CD44, we also confirmed the HA endows the nanoparticles with the ability to target MRSA in subcellular level. In vitro and in vivo murine studies have demonstrated that MNs are capable of delivering HAZ@Fu NPs deep into the dermal layers. And facilitated by the HA coating, HAZ@Fu NPs could target MRSA surviving at the subcellular level. The effective components, such as zinc ions, Fu, and hyaluronic acid could sustainably released, which contributes to antibacterial activity, mitigates inflammation, promotes epithelial regeneration and fosters neovascularization. Through the RNA sequencing of macrophages post co-culture with HAZ@Fu, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis reveals that the biological functionalities associated with wound healing could potentially be facilitated through the PI3K-Akt pathway. The results indicate that the synergistic application of HAZ@Fu NPs with biodegradable MNs may serve as a significant adjunct in the treatment of infected wounds. The intricate mechanisms driving its biological effects merit further investigation.


Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Polissacarídeos , Infecção dos Ferimentos , Camundongos , Animais , Ácido Hialurônico/farmacologia , Fosfatidilinositol 3-Quinases , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cicatrização , Anti-Infecciosos/farmacologia , Infecção dos Ferimentos/tratamento farmacológico , Inflamação
16.
J Nanobiotechnology ; 22(1): 328, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858780

RESUMO

Breast cancer bone metastasis is a terminal-stage disease and is typically treated with radiotherapy and chemotherapy, which causes severe side effects and limited effectiveness. To improve this, Sonodynamic therapy may be a more safe and effective approach in the future. Bacterial outer membrane vesicles (OMV) have excellent immune-regulating properties, including modulating macrophage polarization, promoting DC cell maturation, and enhancing anti-tumor effects. Combining OMV with Sonodynamic therapy can result in synergetic anti-tumor effects. Therefore, we constructed multifunctional nanoparticles for treating breast cancer bone metastasis. We fused breast cancer cell membranes and bacterial outer membrane vesicles to form a hybrid membrane (HM) and then encapsulated IR780-loaded PLGA with HM to produce the nanoparticles, IR780@PLGA@HM, which had tumor targeting, immune regulating, and Sonodynamic abilities. Experiments showed that the IR780@PLGA@HM nanoparticles had good biocompatibility, effectively targeted to 4T1 tumors, promoted macrophage type I polarization and DC cells activation, strengthened anti-tumor inflammatory factors expression, and presented the ability to effectively kill tumors both in vitro and in vivo, which showed a promising therapeutic effect on breast cancer bone metastasis. Therefore, the nanoparticles we constructed provided a new strategy for effectively treating breast cancer bone metastasis.


Assuntos
Membrana Externa Bacteriana , Neoplasias Ósseas , Neoplasias da Mama , Camundongos Endogâmicos BALB C , Feminino , Animais , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Camundongos , Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Linhagem Celular Tumoral , Terapia por Ultrassom/métodos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Células RAW 264.7 , Membrana Celular , Nanopartículas Multifuncionais/química
17.
Lipids Health Dis ; 23(1): 55, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38388371

RESUMO

BACKGROUND: Erectile dysfunction (ED) is closely associated with dyslipidemia; however, it is yet unknown how ED and remnant cholesterol (RC) are related. As such, this research sought to explore the correlation between RC and ED among individuals with diagnosed with diabetes. METHODS: This cross-sectional study used information from 215 males from National Health and Nutrition Examination Survey (NHANES) from 2001 to 2004. RC was calculated as follows: the values of high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) were subtracted from the total cholesterol (TC) value, while ED diagnoses were based on self-reports. Weighted logistic regression analyses using both univariate and multivariate approaches were conducted to assess the correlation between RC and ED. RESULTS: After comprehensive adjustment, multivariable logistic regression models revealed a strong correlation between RC and ED in subjects with diabetes (with an odds ratio (OR) of 7.49 and a 95% confidence interval (CI) of 1.98-28.37; P = 0.004). On categorizing RC into 3 grades (T1-T3), the OR corresponding to higher RC grade increased. Despite the results not reaching statistical significance upon categorization, a consistent and statistically significant trend (P for trend < 0.05) was observed. CONCLUSION: This study indicated a correlation between increased RC levels and a higher prevalence of ED in diabetic males. RC may serve as a promising predictor of ED in individuals with diabetes. However, additional studies are required to confirm these findings.


Assuntos
Diabetes Mellitus , Disfunção Erétil , Hiperlipidemias , Masculino , Humanos , Disfunção Erétil/epidemiologia , Disfunção Erétil/etiologia , Disfunção Erétil/diagnóstico , Inquéritos Nutricionais , Fatores de Risco , Estudos Transversais , Colesterol
18.
BMC Urol ; 24(1): 19, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38268005

RESUMO

AIM: This study aims to compare the perioperative, functional, and oncological outcomes of cryoablation (CA) and partial nephrectomy (PN) for managing small renal masses in patients with solitary kidneys. The study seeks to assess the efficacy and safety of both interventions, evaluating their impact on kidney function and their ability to mitigate cancer recurrence. METHODS: Searches were systematically conducted on PubMed, Scopus, EMBASE, SinoMed, and Google Scholar, identifying seven observational studies. Statistical analysis was performed using Stata v.12.0 and Review Manager version 5.2. Results for dichotomous variables are expressed using odds ratios, and weighted mean differences are used for continuous variables. RESULTS: Our findings revealed that patients undergoing CA experienced significantly shorter operative time (p < 0.0001), reduced estimated blood loss (p < 0.00001), a shorter length of stay (p = 0.0001), and fewer postoperative complications (p = 0.02) compared to those undergoing PN. Although the CA group exhibited a lower transfusion rate (p = 0.69) compared with the PN group, the difference was not statistically significant. The combined data analysis demonstrated a significantly lower increase in serum creatinine levels after surgery in the CA group compared with the PN group (p = 0.003). Similarly, there was a noteworthy decrease in the estimated glomerular filtration rate after surgery in the PN group compared with the CA group (p < 0.0001). While not statistically significant, the CA group showed a lower postoperative dialysis rate (p = 0.11). Regarding oncological outcomes, the analysis revealed no significant differences between CA and PN concerning local recurrence (p = 0.2) and distant metastasis (p = 0.12), respectively. CONCLUSIONS: Our analysis indicates comparable efficacy between PN and CA in controlling tumour recurrence and metastasis. However, CA is associated with superior preservation of renal function, significantly enhanced perioperative outcomes, and fewer postoperative complications. Based on our data, it can be inferred that the scope for applying CA might be expanded to encompass more patients seeking a less invasive treatment option.


Assuntos
Criocirurgia , Rim , Nefrectomia , Humanos , Rim/cirurgia , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia
19.
Proc Natl Acad Sci U S A ; 118(37)2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34503999

RESUMO

The ancestors of marine mammals once roamed the land and independently committed to an aquatic lifestyle. These macroevolutionary transitions have intrigued scientists for centuries. Here, we generated high-quality genome assemblies of 17 marine mammals (11 cetaceans and six pinnipeds), including eight assemblies at the chromosome level. Incorporating previously published data, we reconstructed the marine mammal phylogeny and population histories and identified numerous idiosyncratic and convergent genomic variations that possibly contributed to the transition from land to water in marine mammal lineages. Genes associated with the formation of blubber (NFIA), vascular development (SEMA3E), and heat production by brown adipose tissue (UCP1) had unique changes that may contribute to marine mammal thermoregulation. We also observed many lineage-specific changes in the marine mammals, including genes associated with deep diving and navigation. Our study advances understanding of the timing, pattern, and molecular changes associated with the evolution of mammalian lineages adapting to aquatic life.


Assuntos
Adaptação Fisiológica , Evolução Molecular , Genoma , Genômica , Mamíferos/fisiologia , Filogenia , Termogênese/genética , Animais , Fatores de Transcrição NFI/genética , Fatores de Transcrição NFI/metabolismo , Seleção Genética , Semaforinas/genética , Semaforinas/metabolismo , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
20.
Sensors (Basel) ; 24(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38732862

RESUMO

Online monitoring and real-time feedback on inclusions in molten metal are essential for metal quality control. However, existing methods for detecting aluminum melt inclusions face challenges, including interference, prolonged processing times, and latency. This paper presents the design and development of an online monitoring system for molten metal inclusions. Initially, the system facilitates real-time adjustment of signal acquisition parameters through a multiplexer. Subsequently, it employs a detection algorithm capable of swiftly extracting pulse peaks, with this task integrated into our proprietary host computer software to ensure timely detection and data visualization. Ultimately, we developed a monitoring device integrated with this online monitoring system, enabling the online monitoring of the aluminum alloy filtration process. Our findings indicate that the system can accurately measure the size and concentration of inclusions during the filtration process in real time, offering enhanced detection speed and stability compared to the industrial LiMCA CM (liquid metal cleanliness analyzer continuous monitoring) standard. Furthermore, our evaluation of the filtration process demonstrates that the effectiveness of filtration significantly improves with the increase in inclusion sizes, and the synergistic effect of combining CFF (ceramic foam filter) and MCF (metallics cartridge filter) filtration methods exceeds the performance of the CFF method alone. This system thus provides valuable technical support for optimizing filtration processes and controlling inclusion quality.

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