Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.280
Filtrar
1.
Artigo em Chinês | MEDLINE | ID: mdl-38563175

RESUMO

Objective:To study the difference of postoperative efficacy between two-person three-hand ear endoscopy and microscopic tympanoplasty in patients with chronic suppurative otitis media, and to explore the advantages and disadvantages of two-person three-hand ear endoscopy. Methods:A retrospective study was conducted on 100 patients who underwent tympanoplasty in the Department of Otolaryngology and Head and Neck Surgery of Hunan People's Hospital from April 2019 to March 2023, and they were divided into 2 groups with 50 cases each according to random number table method. Among them, 50 cases underwent endoscopic tympanoplasty in two-person three-hand(group A) and 50 cases underwent routine microscopic tympanoplasty(group B). The operation and postoperative conditions of the two groups were followed up. Results:In group A, the mean operation time was(65.78±18.21) min, the mean intraoperative blood loss was(12.94±4.46) mL, the postoperative pain score was(1.82±0.60) points, and the mean postoperative hospital stay was(2.76±0.72) d. The mean operation time of group B was(89.45±20.38) min, the mean intraoperative blood loss was(22.78±5.74) mL, the postoperative pain score was(2.98±0.85) points, and the mean postoperative hospital stay was(3.82±0.75) d, which with statistical significance between the two groups(P<0.05). Hearing in both groups was significantly improved 6 months after surgery, and the difference was statistically significant before and after surgery(P<0.05), but there was no significant difference between the two groups before surgery and 6 months after surgery(P>0.05). There were 2 cases in group A(4%) and 1 case in group B(2%) complicated with tympanic cord injury during operation, and the difference was not statistically significant(P>0.05). There were 47 cases of A group(94%) of one-time healing of tympanic membrane after operation, 48 cases(96%) of group B, and the difference was not statistically significant(P>0.05). Conclusion:There is no significant difference in cure rate and hearing improvement between two-person three-hand ear endoscopic tympanoplasty and conventional microscope surgery, and the operation time is significantly shortened, the amount of blood loss is less, and the postoperative recovery is faster. It has the advantages of clear operating field, two-person three-hand operation, minimally invasive, and can reach the range of middle ear tympanic sinus and mastoid apex, and the surgical complications are seldom, which is worth promoting.


Assuntos
Otite Média , Timpanoplastia , Humanos , Timpanoplastia/métodos , Perda Sanguínea Cirúrgica , Estudos Retrospectivos , Estudos de Viabilidade , Otite Média/cirurgia , Resultado do Tratamento , Doença Crônica , Endoscopia/métodos , Dor Pós-Operatória
2.
Mol Ther Nucleic Acids ; 35(2): 102165, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571746

RESUMO

Duchenne muscular dystrophy (DMD) is the most prevalent herediatry disease in men, characterized by dystrophin deficiency, progressive muscle wasting, cardiac insufficiency, and premature mortality, with no effective therapeutic options. Here, we investigated whether adenine base editing can correct pathological nonsense point mutations leading to premature stop codons in the dystrophin gene. We identified 27 causative nonsense mutations in our DMD patient cohort. Treatment with adenine base editor (ABE) could restore dystrophin expression by direct A-to-G editing of pathological nonsense mutations in cardiomyocytes generated from DMD patient-derived induced pluripotent stem cells. We also generated two humanized mouse models of DMD expressing mutation-bearing exons 23 or 30 of human dystrophin gene. Intramuscular administration of ABE, driven by ubiquitous or muscle-specific promoters could correct these nonsense mutations in vivo, albeit with higher efficiency in exon 30, restoring dystrophin expression in skeletal fibers of humanized DMD mice. Moreover, a single systemic delivery of ABE with human single guide RNA (sgRNA) could induce body-wide dystrophin expression and improve muscle function in rotarod tests of humanized DMD mice. These findings demonstrate that ABE with human sgRNAs can confer therapeutic alleviation of DMD in mice, providing a basis for development of adenine base editing therapies in monogenic diseases.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38573102

RESUMO

A novel Gram-positive strain, B1T, was isolated from uranium-contaminated soil. The strain was aerobic, rod-shaped, spore-forming, and motile. The strain was able to grow at 20-45 °C, at pH 6.0-9.0, and in the presence of 0-3 % (w/v) NaCl. The complete genome size of the novel strain was 3 853 322 bp. The genomic DNA G+C content was 45.5 mol%. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain B1T has the highest similarity to Aneurinibacillus soli CB4T (96. 71 %). However, the novel strain showed an average nucleotide identity value of 89.02 % and a digital DNA-DNA hybridization value of 37.40 % with strain CB4T based on the genome sequences. The major fatty acids were iso-C15 : 0 and C16 : 0. The predominate respiratory quinone was MK7. Diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, phosphatidylglycerol, unidentified phospholipids, an unidentified aminolipid and an unidentified lipid were identified as the major polar lipids. The phylogenetic, phenotypic, and chemotaxonomic analyses showed that strain B1T represents a novel species of the genus Aneurinibacillus, for which the name Aneurinibacillus uraniidurans sp. nov. is proposed. The type strain is B1T (=GDMCC 1.4080T=JCM 36228T). Experiments have shown that strain B1T demonstrates uranium tolerance.


Assuntos
Ácidos Graxos , Urânio , Composição de Bases , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Bactérias , Solo
4.
Brain Pathol ; : e13261, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602336

RESUMO

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.

5.
Small ; : e2401289, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38593317

RESUMO

2D materials-based broadband photodetectors have extensive applications in security monitoring and remote sensing fields, especially in supersonic aircraft that require reliable performance under extreme high-temperature conditions. However, the integration of large-area heterostructures with 2D materials often involves high-temperature deposition methods, and also limited options and size of substrates. Herein, a liquid-phase spin-coating method is presented based on the interface engineering to prepare larger-area Van der Waals heterojunctions of black phosphorus (BP)/reduced graphene oxide (RGO) films at room temperature on arbitrary substrates of any required size. Importantly, this method avoids the common requirement of high-temperature, and prevents the curling or stacking in 2D materials during the liquid-phase film formation. The BP/RGO films-based devices exhibit a wide spectral photo-response, ranging from the visible of 532 nm to infrared range of 2200 nm. Additionally, due to Van der Waals interface of Schottky junction, the array devices provide infrared detection at temperatures up to 400 K, with an outstanding photoresponsivity (R) of 12 A W-1 and a specific detectivity (D*) of ≈2.4 × 109 Jones. This work offers an efficient approach to fabricate large-area 2D Schottky junction films by solution-coating for high-temperature infrared photodetectors.

6.
Mol Cancer ; 23(1): 74, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582885

RESUMO

BACKGROUND AND AIMS: Sorafenib is a major nonsurgical option for patients with advanced hepatocellular carcinoma (HCC); however, its clinical efficacy is largely undermined by the acquisition of resistance. The aim of this study was to identify the key lncRNA involved in the regulation of the sorafenib response in HCC. MATERIALS AND METHODS: A clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) single-guide RNA (sgRNA) synergistic activation mediator (SAM)-pooled lncRNA library was applied to screen for the key lncRNA regulated by sorafenib treatment. The role of the identified lncRNA in mediating the sorafenib response in HCC was examined in vitro and in vivo. The underlying mechanism was delineated by proteomic analysis. The clinical significance of the expression of the identified lncRNA was evaluated by multiplex immunostaining on a human HCC microtissue array. RESULTS: CRISPR/Cas9 lncRNA library screening revealed that Linc01056 was among the most downregulated lncRNAs in sorafenib-resistant HCC cells. Knockdown of Linc01056 reduced the sensitivity of HCC cells to sorafenib, suppressing apoptosis in vitro and promoting tumour growth in mice in vivo. Proteomic analysis revealed that Linc01056 knockdown in sorafenib-treated HCC cells induced genes related to fatty acid oxidation (FAO) while repressing glycolysis-associated genes, leading to a metabolic switch favouring higher intracellular energy production. FAO inhibition in HCC cells with Linc01056 knockdown significantly restored sensitivity to sorafenib. Mechanistically, we determined that PPARα is the critical molecule governing the metabolic switch upon Linc01056 knockdown in HCC cells and indeed, PPARα inhibition restored the sorafenib response in HCC cells in vitro and HCC tumours in vivo. Clinically, Linc01056 expression predicted optimal overall and progression-free survival outcomes in HCC patients and predicted a better sorafenib response. Linc01056 expression indicated a low FAO level in HCC. CONCLUSION: Our study identified Linc01056 as a critical epigenetic regulator and potential therapeutic target in the regulation of the sorafenib response in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Humanos , Camundongos , Animais , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , RNA Longo não Codificante/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , RNA Guia de Sistemas CRISPR-Cas , PPAR alfa/genética , PPAR alfa/metabolismo , PPAR alfa/uso terapêutico , Proteômica , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica
7.
Nat Commun ; 15(1): 3037, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589472

RESUMO

The directional transformation of carbon dioxide (CO2) with renewable hydrogen into specific carbon-heavy products (C6+) of high value presents a sustainable route for net-zero chemical manufacture. However, it is still challenging to simultaneously achieve high activity and selectivity due to the unbalanced CO2 hydrogenation and C-C coupling rates on complementary active sites in a bifunctional catalyst, thus causing unexpected secondary reaction. Here we report LaFeO3 perovskite-mediated directional tandem conversion of CO2 towards heavy aromatics with high CO2 conversion (> 60%), exceptional aromatics selectivity among hydrocarbons (> 85%), and no obvious deactivation for 1000 hours. This is enabled by disentangling the CO2 hydrogenation domain from the C-C coupling domain in the tandem system for Iron-based catalyst. Unlike other active Fe oxides showing wide hydrocarbon product distribution due to carbide formation, LaFeO3 by design is endowed with superior resistance to carburization, therefore inhibiting uncontrolled C-C coupling on oxide and isolating aromatics formation in the zeolite. In-situ spectroscopic evidence and theoretical calculations reveal an oxygenate-rich surface chemistry of LaFeO3, that easily escape from the oxide surface for further precise C-C coupling inside zeolites, thus steering CO2-HCOOH/H2CO-Aromatics reaction pathway to enable a high yield of aromatics.

8.
Int J Biol Macromol ; : 131670, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38643919

RESUMO

Bacterial infection, hyperinflammation and hypoxia, which can lead to amputation in severe cases, are frequently observed in diabetic wounds, and this has been a critical issue facing the repair of chronic skin injuries. In this study, a copper-based MOF (TAX@HKUST-1) highly loaded with taxifolin (TAX) with a drug loading of 41.94 ±â€¯2.60 % was prepared. In addition, it has excellent catalase activity, and by constructing an oxygen-releasing hydrogel (PTH) system with calcium peroxide (CaO2), it can be used as a nano-enzyme to promote the generation of oxygen from hydrogen peroxide (H2O2) to provide sufficient oxygen to the wound, and at the same time, solve the problem of the oxidative stress damage caused by excess H2O2 to the cells during the oxygen-releasing process. On the other hand, TAX and HKUST-1 in PTH synergistically promoted antimicrobial and anti-oxidative stress properties, and the bacterial inhibition rate against Staphylococcus aureus and Escherichia coli reached 90 %. In vivo experiments have shown that PTH hydrogel is able to treat diabetic skin repair by inhibiting the expression of inflammation-related proteins and promoting epidermal neogenesis, angiogenesis and collagen deposition.

9.
Small Methods ; : e2400241, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644347

RESUMO

All-inorganic lead halide perovskite nanocrystals (NCs) have been widely applied in optoelectronic devices owing to their excellent photoluminescence (PL) properties. However, poor stability upon exposure to water, UV light or heat strongly limits their practical application. Herein, CsPbBr3@Pb-MOF composites with exceptional stability against water, UV light, and heat are synthesized by ultrasonic processing the precursors of lead-based MOF (Pb-MOF), oleylammonium bromide (OAmBr) and cesium oleate (Cs-OA) solutions at room temperature. Pb-MOF can not only provide the lead source for the in situ growth of CsPbBr3 NCs, but also the protective layer of perovskites NCs. The formed CsPbBr3@Pb-MOF composites show a considerable PL quantum yield (PLQY) of 67.8%, and can maintain 90% of the initial PL intensity when immersed in water for 2 months. In addition, the outstanding PL stability against UV light and heat is demonstrated with CsPbBr3 NCs synthesized by the conventional method as a comparison. Finally, a green (light-emitting diode) LED is fabricated using green-emitting CsPbBr3@Pb-MOF composites and exhibits excellent stability without packaging when immersed in water for 30 days. This study provides a practical approach to improve the stability in aqueous phase, which may pave the way for future applications for various optoelectronic devices.

10.
Langmuir ; 40(15): 7992-8001, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38561994

RESUMO

Two-dimensional (2D) materials with a pentagonal structure have many unique physical properties and great potential for applications in electrical, thermal, and optical fields. In this paper, the intrinsic thermal transport properties of 2D pentagonal CX2 (X = N, P, As, and Sb) are comparatively investigated. The results show that penta-CN2 has a high thermal conductivity (302.7 W/mK), while penta-CP2, penta-CAs2, and penta-CSb2 have relatively low thermal conductivities of 60.0, 36.9, and 11.8 W/mK, respectively. The main reason for the high thermal conductivity of penta-CN2 is that the small atomic mass of the N atom is comparable to that of the C atom, resulting in a preferable pentagonal structure with stronger bonds and thus a higher phonon group velocity. The reduction in the thermal conductivity of the other three materials is mainly due to the gradually increased atomic mass from P to Sb, which reduces the phonon group velocity. In addition, the large atomic mass difference does not result in a huge enhancement of the anharmonicity or weakening of the phonon relaxation time. The present work is expected to deepen the understanding of the thermal transport of main group V 2D pentagonal carbons and pave the way for their future applications, also, providing ideas for finding potential thermal management materials.

11.
J Chromatogr A ; 1721: 464858, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38564928

RESUMO

The establishment of an efficient method for the analysis of drug residues in animal urine facilitates the real-time monitoring of drugs used in the production of animal-derived food. A modified QuEChERS extraction-liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for the determination of 47 banned drug and related chemical residues in livestock urine. The sample was extracted with acetonitrile by converting the acid-base environment. The sample cleanup effects of seven solid phase extraction cartridges and two EMR-Lipid products were compared, and three materials, including graphitized carboxyl multi-walled carbon nanotubes (MWCNTs), PSA, and C18, were selected as QuEChERS adsorbents from 24 materials. All analytes showed good linearity, with correlation coefficients (R2) greater than 0.9936. Low limits of quantification could be obtained, ranging from 0.2 to 5.5 ng/mL. The average recoveries at low, medium, and high spiked levels were in the range of 70.8-114.9 %, with intra-day precision ranging from 2.4 % to 11.2 % and inter-day precision ranging from 4.5 % to 16.1 %. Swine urine and bovine urine samples collected from different farms were effectively analyzed using the developed method, and metronidazole was detected in three swine urine samples.


Assuntos
Resíduos de Drogas , Nanotubos de Carbono , Animais , Bovinos , Suínos , Cromatografia Líquida/métodos , Nanotubos de Carbono/química , Espectrometria de Massas em Tandem/métodos , Gado , Extração em Fase Sólida/métodos , Cromatografia Líquida de Alta Pressão/métodos
12.
Bioresour Technol ; 400: 130663, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38583671

RESUMO

The measurement of germination index (GI) in composting is a time-consuming and laborious process. This study employed four machine learning (ML) models, namely Random Forest (RF), Artificial Neural Network (ANN), Support Vector Regression (SVR), and Decision Tree (DT), to predict GI based on key composting parameters. The prediction results showed that the coefficient of determination (R2) for RF (>0.9) and ANN (>0.9) was higher than SVR (<0.6) and DT (<0.8), suggesting that RF and ANN displayed superior predictive performance for GI. The SHapley additive exPlanations value result indicated that composting time, temperature, and pH were the important features contributing to GI. Composting time was found to have the most significant impact on GI. Overall, RF and ANN were suggested as effective tools for predicting GI in composting. This study offers the reliable approach of accurately predicting GI in composting processes, thereby enabling intelligent composting practices.

13.
Angew Chem Int Ed Engl ; : e202403415, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573437

RESUMO

Metal-backboned polymers (MBPs), with a unique backbone consisting of bonded metal atoms, are promising for optic, electric, magnetic, and thermoelectric fields. However, the application of MBP remains relatively understudied. Here, we develop a shear-induced orientation method to construct a flexible nickel-backboned polymer/carbon nanotube (NBP/CNT) thermoelectric hybrid fiber. The obtained fiber demonstrated a power factor of 719.48 µW×m-1×K-2, which is ca. 3.5 times as high as the bare CNT fiber. Remarkably, with the regulation of carrier mobility and carrier concentration of NBP, the hybrid fiber shows simultaneous increases in electrical conductivity and Seebeck coefficient in comparison to the bare CNT fiber. The NBP/CNT fiber can be integrated into fabrics to harvest thermal energy of human body to generate an output voltage of 3.09 mV at a temperature difference of 8 K. This research opens a new avenue for the development of MBPs in power supply.

14.
J Invest Dermatol ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38580105

RESUMO

Interleukin (IL)-6 signaling plays a crucial role in the survival and metastasis of skin cancer. Neural precursor cell expressed developmentally downregulated 4-Like (NEDD4L) acts as a suppressor of IL-6 signaling by targeting glycoprotein 130 (GP130) degradation. However, the effects of the NEDD4L-regulated IL-6/GP130 signaling pathway on skin cancer remain unclear. In this study, protein expression levels of NEDD4L and GP130 were measured in tumor tissues from patients with cutaneous squamous cell carcinoma (cSCC). Skin tumors were induced in wild type (WT) and Nedd4l knockout (KO) mice, and activation of the IL-6/GP130/STAT3 signaling pathway was detected. The results indicated a negative correlation between the protein expression levels of NEDD4L and GP130 in cSCC tissues from patients. Nedd4l deficiency significantly promoted DMBA/TPA-induced skin tumorigenesis and benign-to-malignant conversion by activating the IL-6/GP130/STAT3 signaling pathway, which was abrogated by supplementation with the GP130 inhibitor SC144. Furthermore, our findings suggested that NEDD4L can interact with GP130 and promote its ubiquitination in skin tumors. In conclusion, our results indicate that NEDD4L could act as a tumor suppressor in skin cancer, and inhibition of GP130 could be a potential therapeutic method for treating this disease.

15.
Plant Cell ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581433

RESUMO

The style and stigma at the apical gynoecium are crucial for flowering plant reproduction. However, the mechanisms underlying specification of the apical gynoecium remain unclear. Here, we demonstrate that Class II TEOSINTE BRANCHED 1/CYCLOIDEA/PCF (TCP) transcription factors are critical for apical gynoecium specification in Arabidopsis (Arabidopsis thaliana). The septuple tcp2 tcp3 tcp4 tcp5 tcp10 tcp13 tcp17 (tcpSEP) and duodecuple tcp2 tcp3 tcp4 tcp5 tcp10 tcp13 tcp17 tcp24 tcp1 tcp12 tcp18 tcp16 (tcpDUO) mutants produce narrower and longer styles, while disruption of TCPs and CRABS CLAW (CRC) or NGATHAs (NGAs) in tcpDUO crc or tcpDUO nga1 nga2 nga4 causes the apical gynoecium to be replaced by lamellar structures with indeterminate growth. TCPs are predominantly expressed in the apex of the gynoecium. TCP4 interacts with CRC to synergistically up-regulate the expression level of NGAs, and NGAs further form high-order complexes to control the expression of auxin-related genes in the apical gynoecium by directly interacting with TCP4. Our findings demonstrate that TCP4 physically associates with CRC and NGAs to control auxin biosynthesis in forming fine structures of the apical gynoecium.

16.
BMC Bioinformatics ; 25(1): 146, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38600441

RESUMO

BACKGROUND: The advent of high-throughput technologies has led to an exponential increase in uncharacterized bacterial protein sequences, surpassing the capacity of manual curation. A large number of bacterial protein sequences remain unannotated by Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology, making it necessary to use auto annotation tools. These tools are now indispensable in the biological research landscape, bridging the gap between the vastness of unannotated sequences and meaningful biological insights. RESULTS: In this work, we propose a novel pipeline for KEGG orthology annotation of bacterial protein sequences that uses natural language processing and deep learning. To assess the effectiveness of our pipeline, we conducted evaluations using the genomes of two randomly selected species from the KEGG database. In our evaluation, we obtain competitive results on precision, recall, and F1 score, with values of 0.948, 0.947, and 0.947, respectively. CONCLUSIONS: Our experimental results suggest that our pipeline demonstrates performance comparable to traditional methods and excels in identifying distant relatives with low sequence identity. This demonstrates the potential of our pipeline to significantly improve the accuracy and comprehensiveness of KEGG orthology annotation, thereby advancing our understanding of functional relationships within biological systems.


Assuntos
Proteínas de Bactérias , Processamento de Linguagem Natural , Genoma , Anotação de Sequência Molecular , Sequência de Aminoácidos
17.
EBioMedicine ; 103: 105099, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38604089

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly prevalent and deadly type of cancer, and although pharmacotherapy remains the cornerstone of treatment, therapeutic outcomes are often unsatisfactory. Pharmacological inhibition of mammalian target of rapamycin (mTOR) has been closely associated with HCC regression. METHODS: Herein, we covalently conjugated AZD8055, a potent mTORC1/2 blocker, with a small panel of unsaturated fatty acids via a dynamically activating linkage to enable aqueous self-assembly of prodrug conjugates to form mTOR nanoblockers. Cell-based experiments were carried out to evaluate the effects of the nanoblocker against hepatocellular carcinoma (HCC) cells. The orthotopic and subcutaneous HCC mouse models were established to examine its antitumour activity. FINDINGS: Among several fatty acids as promoieties, linoleic acid-conjugated self-assembling nanoblocker exhibited optimal size distribution and superior physiochemical properties. Compared with free agents, PEGylated AZD8055 nanoblocker (termed AZD NB) was pharmacokinetically optimized after intravenous administration. In vivo investigations confirmed that AZD NB significantly suppressed tumour outgrowth in subcutaneous HCCLM3 xenograft, Hepatoma-22, and orthotopic Hepa1-6 liver tumour models. Strikingly, treatment with AZD NB, but not free agent, increased intratumour infiltration of IFN-γ+CD8+ T cells and CD8+ memory T cells, suggesting a potential role of the mTOR nanoblocker to remodel the tumour microenvironment. Overall, a single conjugation with fatty acid transformed a hydrophobic mTOR blocker into a systemically injectable nanomedicine, representing a facile and generalizable strategy for improving the therapeutic index of mTOR inhibition-based cancer therapy. INTERPRETATION: The mTOR inhibition by chemically engineered nanoblocker presented here had enhanced efficacy against tumours compared with the pristine drug and thus has the potential to improve the survival outcomes of patients with HCC. Additionally, this new nanosystem derived from co-assembling of small-molecule prodrug entities can serve as a delivery platform for the synergistic co-administration of distinct pharmaceutical agents. FUNDING: This work was supported by the National Natural Science Foundation of China (32171368,81721091), the Zhejiang Provincial Natural Science Foundation of China (LZ21H180001), the Jinan Provincial Laboratory Research Project of Microecological Biomedicine (JNL-2022039c and JNL-2022010B), State Key Laboratory for Diagnosis and Treatment of Infectious Diseases (zz202310), and Natural Science Foundation of Shandong Province (ZR2023ZD59).

18.
Cancer Imaging ; 24(1): 50, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605380

RESUMO

OBJECTIVE: The preoperative identification of tumor grade in chondrosarcoma (CS) is crucial for devising effective treatment strategies and predicting outcomes. The study aims to build and validate a CT-based radiomics nomogram (RN) for the preoperative identification of tumor grade in CS, and to evaluate the correlation between the RN-predicted tumor grade and postoperative outcome. METHODS: A total of 196 patients (139 in the training cohort and 57 in the external validation cohort) were derived from three different centers. A clinical model, radiomics signature (RS) and RN (which combines significant clinical factors and RS) were developed and validated to assess their ability to distinguish low-grade from high-grade CS with area under the curve (AUC). Additionally, Kaplan-Meier survival analysis was applied to examine the association between RN-predicted tumor grade and recurrence-free survival (RFS) of CS. The predictive accuracy of the RN was evaluated using Harrell's concordance index (C-index), hazard ratio (HR) and AUC. RESULTS: Size, endosteal scalloping and active periostitis were selected to build the clinical model. Three radiomics features, based on CT images, were selected to construct the RS. Both the RN (AUC, 0.842) and RS (AUC, 0.835) were superior to the clinical model (AUC, 0.776) in the validation set (P = 0.003, 0.040, respectively). A correlation between Nomogram score (Nomo-score, derived from RN) and RFS was observed through Kaplan-Meier survival analysis in the training and test cohorts (log-rank P < 0.050). Patients with high Nomo-score tumors were 2.669 times more likely to suffer recurrence than those with low Nomo-score tumors (HR, 2.669, P < 0.001). CONCLUSIONS: The CT-based RN performed well in predicting both the histologic grade and outcome of CS.


Assuntos
Neoplasias Ósseas , Condrossarcoma , Humanos , Nomogramas , 60570 , Condrossarcoma/diagnóstico por imagem , Neoplasias Ósseas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Estudos Retrospectivos
19.
J Org Chem ; 89(8): 5883-5895, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38600052

RESUMO

By creating an unsymmetric double Michael acceptor 1, we were able to synthesize the nonaromatic-fused bicyclic furo[2,3-b]pyrrole nucleus using a domino Michael/oxa-Michael reaction. Adopting benzoyl acetonitrile 2d (CN as the electron-withdrawing group) as a substrate, we discovered a (DHQ)2AQN-catalyzed method for high diastereo- and enantioselectivity of those products. The reaction path has been determined by isolating the reaction intermediates, and density functional theory calculations support these findings. Beyond providing a synthetic approach, this work illustrated the compounds' possible use in antitumor activity.

20.
Chemosphere ; 357: 141943, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38621492

RESUMO

In this study, bentonite supporting phosphorus-doped Fe2MnO4 (BPF) was synthesized and applied for PMS activation to degrade TCE. Morphology and structure characterization results indicated the successfully synthesized of BPF, and the BPF/PMS system not only featured high TCE removal (97.4%) but also high reaction rate constant (kobs = 0.0554 min-1) and PMS utilization (70.4%, kobs = 0.0228 min-1). According to the results of various experiments, massive oxygen vacancies on P-Fe2MnO4 alter its charge balance and facilitate the electron transfer process named adjacent transfer (direct electron capture by adsorbed PMS from adjacent TCE). Mn(III) is the main adsorption site for PMS, and the hydroxyl groups on the catalyst (Fe sites of P-Fe2MnO4, Si and Al sites of bentonite) can also offer binding sites for PMS. The hydrogen-bonded PMS on Fe(III) and Mn(III) sites will subsequently accept the discharged electrons to generate free radicals and high-valent metal species. Meanwhile, electron loss of HSO5- that chemically bonded to hydroxyl groups on bentonite will generate SO5•-, which will further produce 1O2 through self-bonding. the active species on the catalyst surface contribute 65% of TCE degradation in the heterogeneous catalytic oxidation system.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...