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1.
Nat Commun ; 15(1): 3754, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704395

RESUMO

Due to their responsiveness to modulation by external direct current fields, dielectric tunable materials are extensively utilized in integrated components, such as ferroelectric phase shifters. Barium strontium titanate ceramics have been considered the most potential tunable materials for a long time. However, the significant dielectric loss and high voltage drive have limited their further applications. Recently, Bi6Ti5WO22 ceramic has regained attention for its high dielectric tunability with low loss. In this study, we judiciously introduce Nb5+ with a larger ionic radius, replacing Ti4+ and W6+. This successful substitution enables the modulation of the phase transition temperature of Bi6Ti5WO22 ceramics to room temperature, resulting in superior tunable properties. Specifically, the 0.7Bi6Ti5WO22-0.3Bi6Ti4Nb2O22 ceramics exhibit giant tunability (~75.6%) with ultralow loss (<0.002) under a low electric field (1.5 kV/mm). This tunability is twice that of barium strontium titanate ceramics with a similar dielectric constant and only one-tenth of the loss. Neutron powder diffraction and transmission-electron-microscopy illustrate the nanodomains and micro-strains influenced by ion substitution. Density functional theory simulation calculations reveal the contribution of ion substitution to polarization. The research provides an ideal substitute for tunable material and a general strategy for adjusting phase transition temperature to improve dielectric properties.

2.
Opt Lett ; 49(9): 2341-2344, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691714

RESUMO

In the fields of biomedicine and microfluidics, the non-contact capture, manipulation, and spin of micro-particles hold great importance. In this study, we propose a programmable non-contact manipulation technique that utilizes photoacoustic effect to spin and transport living shrimp eggs. By directing a modulated pulsed laser toward a liquid-covered stainless-steel membrane, we can excite patterned Lamb waves within the membrane. These Lamb waves occur at the interface between the membrane and the liquid, enabling the manipulation of nearby particles. Experimental results demonstrate the successful capture, spin, and transport of shrimp eggs in diameter of 220 µm over a distance of about 5 mm. Calculations indicate that the acoustic radiation force and torque generated by our photoacoustic manipulation system are more than 299.5 nN and 41.0 nN·mm, respectively. The system surpasses traditional optical tweezers in terms of force and traditional acoustic tweezers in terms of flexibility. Consequently, this non-contact manipulation system significantly expands the possibilities for applications in various fields, including embryo screening, cell manipulation, and microfluidics.


Assuntos
Óvulo , Técnicas Fotoacústicas , Animais , Técnicas Fotoacústicas/métodos , Pressão , Pinças Ópticas , Penaeidae
3.
Radiol Cardiothorac Imaging ; 6(3): e230281, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38695743

RESUMO

Purpose To describe the clinical presentation, comprehensive cardiac MRI characteristics, and prognosis of individuals with predisposed heart failure with preserved ejection fraction (HFpEF). Materials and Methods This prospective cohort study (part of MISSION-HFpEF [Multimodality Imaging in the Screening, Diagnosis, and Risk Stratification of HFpEF]; NCT04603404) was conducted from January 1, 2019, to September 30, 2021, and included individuals with suspected HFpEF who underwent cardiac MRI. Participants who had primary cardiomyopathy and primary valvular heart disease were excluded. Participants were split into a predisposed HFpEF group, defined as HFpEF with normal natriuretic peptide levels based on an HFA-PEFF (Heart Failure Association Pretest Assessment, Echocardiography and Natriuretic Peptide, Functional Testing, and Final Etiology) score of 4 from the latest European Society of Cardiology guidelines, and an HFpEF group (HFA-PEFF score of ≥ 5). An asymptomatic control group without heart failure was also included. Clinical and cardiac MRI-based characteristics and outcomes were compared between groups. The primary end points were death, heart failure hospitalization, or stroke. Results A total of 213 participants with HFpEF, 151 participants with predisposed HFpEF, and 100 participants in the control group were analyzed. Compared with the control group, participants with predisposed HFpEF had worse left ventricular remodeling and function and higher systemic inflammation. Compared with participants with HFpEF, those with predisposed HFpEF, whether obese or not, were younger and had higher plasma volume, lower prevalence of atrial fibrillation, lower left atrial volume index, and less impaired left ventricular global longitudinal strain (-12.2% ± 2.8 vs -13.9% ± 3.1; P < .001) and early-diastolic global longitudinal strain rate (eGLSR, 0.52/sec ± 0.20 vs 0.57/sec ± 0.15; P = .03) but similar prognosis. Atrial fibrillation occurrence (hazard ratio [HR] = 3.90; P = .009), hemoglobin level (HR = 0.94; P = .001), and eGLSR (per 0.2-per-second increase, HR = 0.28; P = .002) were independently associated with occurrence of primary end points in participants with predisposed HFpEF. Conclusion Participants with predisposed HFpEF showed relatively unique clinical and cardiac MRI features, warranting greater clinical attention. eGLSR should be considered as a prognostic factor in participants with predisposed HFpEF. Keywords: Heart Failure with Preserved Ejection Fraction, Normal Natriuretic Peptide Levels, Cardiovascular Magnetic Resonance, Myocardial Strain, Prognosis Clinical trial registration no. NCT04603404 Supplemental material is available for this article. © RSNA, 2024.


Assuntos
Insuficiência Cardíaca , Peptídeos Natriuréticos , Volume Sistólico , Humanos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/sangue , Estudos Prospectivos , Feminino , Volume Sistólico/fisiologia , Masculino , Idoso , Peptídeos Natriuréticos/sangue , Pessoa de Meia-Idade , Imagem Cinética por Ressonância Magnética/métodos , Prognóstico , Imageamento por Ressonância Magnética
4.
ISA Trans ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38714374

RESUMO

This research presents a novel approach called 'Time-to-target-based multi-missile spatio-temporal cooperative guidance' This approach enables the simultaneous guidance of multiple missiles, allowing them to intercept a maneuvering target from different terminal intercept angles to maximize damage. The article introduces a finite-time optimal cooperative guidance technique to reduce the load on missile engines in the line-of-sight (LOS) direction. It proposes a time-varying sliding mode guidance scheme, which is parameterized by the remaining flight time, for both longitudinal and lateral LOS directions. The scheme helps prevent excessive initial acceleration in the longitudinal and lateral LOS directions while ensuring intercept angle constraints. The time-varying cooperative guidance law proposed in this study enables the simultaneous interception of a maneuvering target with different terminal intercept angles at the moment of terminal intercept. The numerical simulation results indicate that the multi-missile spatio-temporal cooperative guidance method is effective, superior, and robust. The method enables multiple missiles to achieve the minimum acceptable intercept distance at different terminal intercept angles while optimizing fuel in the LOS direction.

5.
Regen Ther ; 27: 419-433, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38694444

RESUMO

Regarded as the most promising treatment modality for retinal degenerative diseases, retinal pigment epithelium cell replacement therapy holds significant potential. Common retinal degenerative diseases, including Age-related Macular Degeneration, are frequently characterized by damage to the unit comprising photoreceptors, retinal pigment epithelium, and Bruch's membrane. The selection of appropriate tissue engineering materials, in conjunction with retinal pigment epithelial cells, for graft preparation, can offer an effective treatment for retinal degenerative diseases. This article presents an overview of the research conducted on retinal pigment epithelial cell tissue engineering, outlining the challenges and future prospects.

7.
Br J Pharmacol ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589338

RESUMO

BACKGROUND AND PURPOSE: It is well acknowledged that tobacco-derived lung carcinogens can induce lung injury and even lung cancer through a complex mechanism. MicroRNAs (MiRNAs) are differentially expressed in tobacco-derived carcinogen nicotine-derived nitrosamine ketone (NNK)-treated A/J mice. EXPERIMENTAL APPROACH: RNA sequencing was used to detect the level of long non-coding RNAs (lncRNAs). Murine and human lung normal and cancer cells were used to evaluate the function of lncRNA XIST and miR-328-3p in vitro, and NNK-treated A/J mice were used to test their function in vivo. In vivo levels of miR-328-3p and lncRNA XIST were analysed, using in situ hybridization. miR-328-3p agomir and lncRNA XIST-specific siRNA were used to manipulate in vivo levels of miR-328-3p and lncRNA XIST in A/J mice. KEY RESULTS: LncRNA XIST was up-regulated in NNK-induced lung injury and dominated the NNK-induced ectopic miRNA expression in NNK-induced lung injury both in vitro and in vivo. Either lncRNA XIST silencing or miR-328-3p overexpression exerted opposing effects in lung normal and cancer cells regarding cell migration. LncRNA XIST down-regulated miR-328-3p levels as a miRNA sponge, and miR-328-3p targeted the 3'-UTR of FZD7 mRNA, which is ectopically overexpressed in lung cancer patients. Both in vivo lncRNA XIST silencing and miR-328 overexpression could rescue NNK-induced lung injury and aberrant overexpression of the lung cancer biomarker CK19 in NNK-treated A/J mice. CONCLUSIONS AND IMPLICATIONS: Our results highlight the promotive effect of lncRNA XIST in NNK-induced lung injury and elucidate its post-transcriptional mechanisms, indicating that targeting lncRNA XIST/miR-328-3p could be a potential therapeutic strategy to prevent tobacco carcinogen-induced lung injury in vivo.

8.
Ying Yong Sheng Tai Xue Bao ; 35(3): 705-712, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38646758

RESUMO

The composition and stability of soil aggregates are important indicators for measuring soil quality, which would be affected by land use changes. Taking wetlands with different returning years (2 and 15 years) in the Yellow River Delta as the research object, paddy fields and natural wetlands as control, we analyzed the changes in soil physicochemical properties and soil aggregate composition. The results showed that soil water content, total organic carbon, dissolved organic carbon and total phosphorus of the returning soil (0-40 cm) showed an overall increasing trend with returning period, while soil pH and bulk density was in adverse. There was no significant change in clay content, electrical conductivity, and total nitrogen content. The contents of macro-aggregates and micro-aggregates showed overall increasing and decreasing trend with returning period, respectively. The stability of aggregates in the topsoil (0-10 cm) increased with returning years. Geometric mean diameter and mean weight diameter increased by 8.9% and 40.4% in the 15th year of returning, respectively, while the mass proportion of >2.5 mm fraction decreased by 10.5%. There was no effect of returning on aggregates in subsoil (10-40 cm). Our results indicated that returning paddy field to wetland in the Yellow River Delta would play a positive role in improving soil structure and aggregate stability.


Assuntos
Oryza , Rios , Solo , Áreas Alagadas , Solo/química , China , Rios/química , Oryza/crescimento & desenvolvimento , Oryza/química , Monitoramento Ambiental , Agricultura/métodos , Fósforo/análise , Fósforo/química , Carbono/análise , Carbono/química
9.
Nat Commun ; 15(1): 3250, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627385

RESUMO

Optical and acoustic tweezers, despite operating on different physical principles, offer non-contact manipulation of microscopic and mesoscopic objects, making them essential in fields like cell biology, medicine, and nanotechnology. The advantages and limitations of optical and acoustic manipulation complement each other, particularly in terms of trapping size, force intensity, and flexibility. We use photoacoustic effects to generate localized Lamb wave fields capable of mapping arbitrary laser pattern shapes. By using localized Lamb waves to vibrate the surface of the multilayer membrane, we can pattern tens of thousands of microscopic particles into the desired pattern simultaneously. Moreover, by quickly and successively adjusting the laser shape, microparticles flow dynamically along the corresponding elastic wave fields, creating a frame-by-frame animation. Our approach merges the programmable adaptability of optical tweezers with the potent manipulation capabilities of acoustic waves, paving the way for wave-based manipulation techniques, such as microparticle assembly, biological synthesis, and microsystems.

10.
Animals (Basel) ; 14(8)2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38672293

RESUMO

Identifying genetic markers of economically valuable traits has practical benefits for the meat goat industry. To better understand the genomic variations influencing body conformation traits, a genome-wide association study was performed on Tashi goats, an indigenous Chinese goat breed. A total of 155 Tashi goats were phenotyped for eight body conformation traits: body height, body length, chest depth, chest width, chest girth, rump width, rump height, and cannon bone circumference. Then, 100 Tashi goats were randomly selected for whole-genome sequencing and genotyped. We obtained 1676.4 Gb of raw data with an average sequencing depth of 6.2X. Clean reads were aligned to the ARS1.2 reference genome, and 11,257,923 single nucleotide polymorphisms (SNPs) were identified. The structure analysis showed that these Tashi goats were almost not genetically related. The 109, 20, 52, 14, 62, 51, 70, and 7 SNPs were significantly associated with body height, body length, chest depth, chest width, chest girth, rump width, rump height, and cannon bone circumference. Within the ±500 kb region of significant SNPs, 183 genes were annotated. The most significantly enriched KEGG pathway was "olfactory transduction", and the most significantly enriched gene ontology (GO) terms were "cellular process", "cellular anatomical entity", and "molecular transducer activity". Interestingly, we found several SNPs on chromosomes 10 and 11 that have been identified multiple times for all eight body conformation traits located in two fragments (114 kb and 1.03 Mb). In chr.10:25988403-26102739, the six SNPs were tightly linked, the TACTAG genotype was the highest at 91.8%, and the FNTB (Farnesyltransferase, CAAX Box Beta) and CHURC1 (Churchill Domain Containing 1) genes were located. In chr.11:88216493-89250659, ten SNPs were identified with several dependent linkage disequilibrium (LD) blocks, and seven related genes were annotated, but no significant SNP was located in them. Our results provide valuable biological information for improving growth performance with practical applications for genomic selection in goats.

11.
Nat Cell Biol ; 26(5): 770-783, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38600236

RESUMO

DNA-protein crosslinks (DPCs) arise from enzymatic intermediates, metabolism or chemicals like chemotherapeutics. DPCs are highly cytotoxic as they impede DNA-based processes such as replication, which is counteracted through proteolysis-mediated DPC removal by spartan (SPRTN) or the proteasome. However, whether DPCs affect transcription and how transcription-blocking DPCs are repaired remains largely unknown. Here we show that DPCs severely impede RNA polymerase II-mediated transcription and are preferentially repaired in active genes by transcription-coupled DPC (TC-DPC) repair. TC-DPC repair is initiated by recruiting the transcription-coupled nucleotide excision repair (TC-NER) factors CSB and CSA to DPC-stalled RNA polymerase II. CSA and CSB are indispensable for TC-DPC repair; however, the downstream TC-NER factors UVSSA and XPA are not, a result indicative of a non-canonical TC-NER mechanism. TC-DPC repair functions independently of SPRTN but is mediated by the ubiquitin ligase CRL4CSA and the proteasome. Thus, DPCs in genes are preferentially repaired in a transcription-coupled manner to facilitate unperturbed transcription.


Assuntos
DNA Helicases , Enzimas Reparadoras do DNA , Reparo do DNA , Proteínas de Ligação a Poli-ADP-Ribose , Proteólise , RNA Polimerase II , Transcrição Gênica , Enzimas Reparadoras do DNA/metabolismo , Enzimas Reparadoras do DNA/genética , Humanos , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/genética , DNA Helicases/metabolismo , DNA Helicases/genética , RNA Polimerase II/metabolismo , RNA Polimerase II/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , DNA/metabolismo , DNA/genética , Células HEK293 , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Dano ao DNA , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas de Transporte , Receptores de Interleucina-17
12.
Bioorg Chem ; 147: 107335, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38583250

RESUMO

Fifty compounds including seven undescribed (1, 13, 18-20, 30, 31) and forty-three known (2-12, 14-17, 21-29, 32-50) ones were isolated from the extract of the twigs and leaves of Aglaia odorata with anti-neuroinflammatory activities. Their structures were determined by a combination of spectral analysis and calculated spectra (ECD and NMR). Among them, compounds 13-25 were found to possess tertiary amide bonds, with compounds 16, 17, and 19-21 existing detectable cis/trans mixtures in 1H NMR spectrum measured in CDCl3. Specifically, the analysis of the cis-trans isomerization equilibrium of tertiary amides in compounds 19-24 was conducted using NMR spectroscopy and quantum chemical calculations. Bioactivity evaluation showed that the cyclopenta[b]benzofuran derivatives (2-6, 8, 10, 12) could inhibit nitric oxide production at the nanomolar concentration (IC50 values ranging from 2 to 100 nM) in lipopolysaccharide-induced BV-2 cells, which were 413-20670 times greater than that of the positive drug (minocycline, IC50 = 41.34 µM). The cyclopenta[bc]benzopyran derivatives (13-16), diterpenoids (30-35), lignan (40), and flavonoids (45, 47, 49, 50) also demonstrated significant inhibitory activities with IC50 values ranging from 1.74 to 38.44 µM. Furthermore, the in vivo anti-neuroinflammatory effect of rocaglaol (12) was evaluated via immunofluorescence, qRT-PCR, and western blot assays in the LPS-treated mice model. The results showed that rocaglaol (12) attenuated the activation of microglia and decreased the mRNA expression of iNOS, TNF-α, IL-1ß, and IL-6 in the cortex and hippocampus of mice. The mechanistic study suggested that rocaglaol might inhibit the activation of the NF-κB signaling pathway to relieve the neuroinflammatory response.


Assuntos
Aglaia , Lipopolissacarídeos , Óxido Nítrico , Animais , Camundongos , Aglaia/química , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico/metabolismo , Estrutura Molecular , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Masculino , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Benzofuranos/farmacologia , Benzofuranos/química , Benzofuranos/isolamento & purificação , Linhagem Celular , Folhas de Planta/química
13.
Biomater Sci ; 12(8): 2096-2107, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38441146

RESUMO

Neuroinflammation is a common feature in various neurological disorders. Understanding neuroinflammation and neuro-immune interactions is of significant importance. However, the intercellular interactions in the inflammatory model are intricate. Microfluidic chips, with their complex micrometer-scale structures and real-time observation capabilities, offer unique advantages in tackling these complexities compared to other techniques. In this study, microfluidic chip technology was used to construct a microarray physical barrier structure with 15 µm spacing, providing well-defined cell growth areas and clearly delineated interaction channels. Moreover, an innovative hydrophilic treatment process on the glass surface facilitated long-term co-culture of cells. The developed neuroinflammation model on the chip revealed that SH-SY5Y cytotoxicity was predominantly influenced by co-cultured THP-1 cells. The co-culture model fostered complex interactions that may exacerbate cytotoxicity, including irregular morphological changes of cells, cell viability reduction, THP-1 cell migration, and the release of inflammatory factors. The integration of the combinatorial cell-cell interaction chip not only offers a clear imaging detection platform but also provides diverse data on cell migration distance, migration direction, and migration angle. Furthermore, the designed ample space for cell culture, along with microscale channels with fluid characteristics, allow for the study of inflammatory factor distribution patterns on the chip, offering vital theoretical data on biological relevance that conventional experiments cannot achieve. The fabricated user-friendly, reusable, and durable co-culture chip serves as a valuable in vitro tool, providing an intuitive platform for gaining insights into the complex mechanisms underlying neuroinflammation and other interacting models.


Assuntos
Neuroblastoma , Doenças Neuroinflamatórias , Humanos , Técnicas de Cultura de Células , Técnicas de Cocultura , Comunicação Celular
14.
Br J Haematol ; 204(4): 1307-1324, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38462771

RESUMO

Multiple myeloma (MM) is the second most common malignant haematological disease with a poor prognosis. The limit therapeutic progress has been made in MM patients with cancer relapse, necessitating deeper research into the molecular mechanisms underlying its occurrence and development. A genome-wide CRISPR-Cas9 loss-of-function screening was utilized to identify potential therapeutic targets in our research. We revealed that COQ2 plays a crucial role in regulating MM cell proliferation and lipid peroxidation (LPO). Knockout of COQ2 inhibited cell proliferation, induced cell cycle arrest and reduced tumour growth in vivo. Mechanistically, COQ2 promoted the activation of the MEK/ERK cascade, which in turn stabilized and activated MYC protein. Moreover, we found that COQ2-deficient MM cells increased sensitivity to the LPO activator, RSL3. Using an inhibitor targeting COQ2 by 4-CBA enhanced the sensitivity to RSL3 in primary CD138+ myeloma cells and in a xenograft mouse model. Nevertheless, co-treatment of 4-CBA and RSL3 induced cell death in bortezomib-resistant MM cells. Together, our findings suggest that COQ2 promotes cell proliferation and tumour growth through the activation of the MEK/ERK/MYC axis and targeting COQ2 could enhance the sensitivity to ferroptosis in MM cells, which may be a promising therapeutic strategy for the treatment of MM patients.


Assuntos
Mieloma Múltiplo , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Proliferação de Células , Sistemas CRISPR-Cas , Modelos Animais de Doenças , Peroxidação de Lipídeos , Quinases de Proteína Quinase Ativadas por Mitógeno/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico
15.
Antiviral Res ; 225: 105872, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38556058

RESUMO

The antiviral activity of interferon gamma (IFNγ) against hepatitis B virus (HBV) was demonstrated both in vivo and in vitro in a previous study. IFNγ can suppress HBV replication by accelerating the decay of replication-competent nucleocapsids of HBV. However, in this study, we found that the direct application of the mouse IFNγ (mIFNγ) expression plasmid to the liver of an HBV hydrodynamic injection (HI) mouse model led to the persistence of HBV, as indicated by sustained HBsAg and HBeAg levels in the serum as well as an increased percentage of the HBsAg positive mice, whereas the level of HBV DNA in the serum and the expression of HBcAg in the liver were inhibited at the early stage after HI. Meanwhile, we found that the productions of both HBcAb and HBsAb were suppressed after the application of mIFNγ. In addition, we found that HBV could be effectively inhibited in mice immunized with HBsAg expression plasmid before the application of mIFNγ. Furthermore, mIFNγ showed antiviral effect and promoted the production of HBsAb when the mice subjected to the core-null HBV plasmid. These results indicate that the application of mIFNγ in the HBV HI mouse model, the mice showed defective HBcAg-specific immunity that impeded the production of HBcAb and HBsAb, finally allowing the persistence of the virus. Moreover, IFNγ-induced negative immune regulatory factors also play an important role in virus persistence.


Assuntos
Vírus da Hepatite B , Hepatite B , Animais , Camundongos , Interferon gama/metabolismo , Antígenos do Núcleo do Vírus da Hepatite B/genética , Antígenos de Superfície da Hepatite B , Fígado , Anticorpos Anti-Hepatite B , Antivirais/farmacologia , Replicação Viral
16.
Artigo em Inglês | MEDLINE | ID: mdl-38430179

RESUMO

Background: With the development of endoscopic technology, the application of upper endoscopy can quickly target the lesion site of patients with peptic ulcer complicated with upper gastrointestinal bleeding. Objective: This study aims to discuss the clinical effect of octreotide combined with upper endoscopy in treating peptic ulcer complicated with upper gastrointestinal hemorrhage. Methods: A total of 82 patients diagnosed with peptic ulcer complicated with upper gastrointestinal hemorrhage were recruited as study objects in the researchers' hospital. According to the treatment method, this retrospective study divided the patients into a control group (n=41, receiving adrenaline injection under upper endoscopy only) and a treatment group (n=41, receiving adrenaline injection under upper endoscopy and Octreotide intravenously). Results: After treatment, the volume of blood loss, average hemostasis time, hospital stay, and time of occult blood turning negative in the treatment group were shorter than those in the control group (P < .05). After treatment, the clinical efficacy of the treatment group was better than that of the control group (P < .05). The levels of prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) levels in the treatment group were lower than those in the control group, with significant differences (P < .05). Conclusion and Relevance: Combining octreotide and upper endoscopy has affirmative efficacy and good hemostatic effect on treating peptic ulcer complicated with upper gastrointestinal hemorrhage with less pain and short recovery time, which is worthy of clinical application.

17.
ChemMedChem ; : e202300721, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38503694

RESUMO

Hasubanan alkaloids represent a distinct class of alkaloids bearing a structural resemblance to morphine, predominantly found in herbals of the Stephania genus. Their intriguing molecular architecture and potential analgesic properties have captured the interest of medicinal chemists worldwide. This review meticulously examines the natural distribution, structural characteristics, biosynthetic pathways, synthetic methodologies, and biological activities of hasubanans.

18.
CNS Neurosci Ther ; 30(3): e14693, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38544365

RESUMO

Cerebral metabolic dysfunction is a critical pathological hallmark observed in the aftermath of traumatic brain injury (TBI), as extensively documented in clinical investigations and experimental models. An in-depth understanding of the bioenergetic disturbances that occur following TBI promises to reveal novel therapeutic targets, paving the way for the timely development of interventions to improve patient outcomes. The 13C isotope tracing technique represents a robust methodological advance, harnessing biochemical quantification to delineate the metabolic trajectories of isotopically labeled substrates. This nuanced approach enables real-time mapping of metabolic fluxes, providing a window into the cellular energetic state and elucidating the perturbations in key metabolic circuits. By applying this sophisticated tool, researchers can dissect the complexities of bioenergetic networks within the central nervous system, offering insights into the metabolic derangements specific to TBI pathology. Embraced by both animal studies and clinical research, 13C isotope tracing has bolstered our understanding of TBI-induced metabolic dysregulation. This review synthesizes current applications of isotope tracing and its transformative potential in evaluating and addressing the metabolic sequelae of TBI.


Assuntos
Lesões Encefálicas Traumáticas , Animais , Humanos , Lesões Encefálicas Traumáticas/metabolismo , Metabolismo Energético , Isótopos
19.
Quant Imaging Med Surg ; 14(3): 2267-2279, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38545039

RESUMO

Background: Diabetes mellitus can occur after acute pancreatitis (AP), but the accurate quantitative methods to predict post-acute pancreatitis diabetes mellitus (PPDM-A) are lacking. This retrospective study aimed to establish a radiomics model based on contrast-enhanced computed tomography (CECT) for predicting PPDM-A. Methods: A total of 374 patients with first-episode AP were retrospectively enrolled from two tertiary referral centers. There were 224 patients in the training cohort, 56 in the internal validation cohort, and 94 in the external validation cohort, and there were 86, 22, and 27 patients with PPDM-A in these cohorts, respectively. The clinical characteristics were collected from the hospital information system. A total of 2,398 radiomics features, including shape-based features, first-order histogram features, high order textural features, and transformed features, were extracted from the arterial- and venous-phase CECT images. Intraclass correlation coefficients were used to assess the intraobserver reliability and interobserver agreement. Random forest-based recursive feature elimination, collinearity analysis, and least absolute shrinkage and selection operator (LASSO) were used for selecting the final features. Three classification methods [eXtreme Gradient Boosting (XGBoost), Adaptive Boosting, and Decision Tree] were used to build three models and performances of the three models were compared. Each of the three classification methods were used to establish the clinical model, radiomics model, and combined model for predicting PPDM-A, resulting in a total of nine classifiers. The predictive performances of the models were evaluated by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1-score. Results: Eleven radiomics features were selected after a reproducibility test and dimensionality reduction. Among the three classification methods, the XGBoost classifier showed better and more consistent performances. The AUC of the XGBoost's radiomics model to predict PPDM-A in the training, internal, and external cohorts was good (0.964, 0.901, and 0.857, respectively). The AUC of the XGBoost's combined model to predict PPDM-A in the training, internal, and external cohorts was good (0.980, 0.901, and 0.882, respectively). The AUC of the XGBoost's clinical model to predict PPDM-A in the training, internal, and external cohorts did not perform well (0.685, 0.733, and 0.619, respectively). In the external validation cohort, the AUC of the XGBoost's radiomics model was significantly higher than that of the clinical model (0.857 vs. 0.619, P<0.001), but there was no significant difference between the combined and radiomics models (0.882 vs. 0.857, P=0.317). Conclusions: The radiomics model based on CECT performs well and can be used as an early quantitative method to predict the occurrence of PPDM-A.

20.
Eur Radiol ; 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38421414

RESUMO

OBJECTIVES: We aimed to explore imaging features including tissue characterization and myocardial deformation in diabetic heart failure with preserved ejection fraction (HFpEF) patients by magnetic resonance imaging (MRI) and investigate its prognostic value for adverse outcomes. MATERIALS AND METHODS: Patients with HFpEF who underwent cardiac MRI between January 2010 and December 2016 were enrolled. Feature-tracking (FT) analysis and myocardial fibrosis were assessed by cardiac MRI. Cox proportional regression analysis was performed to determine the association between MRI variables and primary outcomes. Primary outcomes were all-cause death or heart failure hospitalization during the follow-up period. RESULTS: Of the 335 enrolled patients with HFpEF, 191 had diabetes mellitus (DM) (mean age: 58.7 years ± 10.8; 137 men). During a median follow-up of 10.2 years, 91 diabetic HFpEF and 56 non-diabetic HFpEF patients experienced primary outcomes. DM was a significant predictor of worse prognosis in HFpEF. In diabetic HFpEF, the addition of conventional imaging variables (left ventricular ejection fraction, left atrial volume index, extent of late gadolinium enhancement (LGE)) and global longitudinal strain (GLS) resulted in a significant increase in the area under the receiver operating characteristic curve (from 0.693 to 0.760, p < 0.05). After adjustment for multiple clinical and imaging variables, each 1% worsening in GLS was associated with a 9.8% increased risk of adverse events (p = 0.004). CONCLUSIONS: Diabetic HFpEF is characterized by more severely impaired strains and myocardial fibrosis, which is identified as a high-risk HFpEF phenotype. In diabetic HFpEF, comprehensive cardiac MRI provides incremental value in predicting prognosis. Particularly, MRI-FT measurement of GLS is an independent predictor of adverse outcome in diabetic HFpEF. CLINICAL RELEVANCE STATEMENT: Our findings suggested that MRI-derived variables, especially global longitudinal strain, played a crucial role in risk stratification and predicting worse prognosis in diabetic heart failure with preserved ejection fraction, which could assist in identifying high-risk patients and guiding therapeutic decision-making. KEY POINTS: • Limited data are available on the cardiac MRI features of diabetic heart failure with preserved ejection fraction, including myocardial deformation and tissue characterization, as well as their incremental prognostic value. • Diabetic heart failure with preserved ejection fraction patients was characterized by more impaired strains and myocardial fibrosis. Comprehensive MRI, including tissue characterization and global longitudinal strain, provided incremental value for risk prediction. • MRI served as a valuable tool for identifying high-risk patients and guiding clinical management in diabetic heart failure with preserved ejection fraction.

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