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1.
Bioorg Chem ; 147: 107310, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38583249

RESUMO

Using the licochalcone moiety as a lead compound scaffold, 16 novel imidazole-chalcone derivatives were designed and synthesized as microtubule protein polymerization inhibitors. The proliferation inhibitory activities of the derivatives against SiHa (human cervical squamous cell carcinoma), C-33A (human cervical cancer), HeLa (human cervical cancer), HeLa/DDP (cisplatin-resistant human cervical cancer), and H8 (human cervical epithelial immortalized) cells were evaluated. Compound 5a exhibited significant anticancer activity with IC50 values ranging from 2.28 to 7.77 µM and a resistance index (RI) of 1.63, while showing minimal toxicity to normal H8 cells. When compound 5a was coadministered with cisplatin, the RI of cisplatin to HeLa/DDP cells decreased from 6.04 to 2.01, while compound 5a enhanced the fluorescence intensity of rhodamine 123 in HeLa/DDP cells. Further studies demonstrated that compound 5a arrested cells at the G2/M phase, induced apoptosis, reduced colony formation, inhibited cell migration, and inhibited cell invasion. Preliminary mechanistic studies revealed that compound 5a decreased the immunofluorescence intensity of α-/ß-tubulin in cancer cells, reduced the expression of polymerized α-/ß-tubulin, and increased the expression of depolymerized α-/ß-tubulin. Additionally, the molecular docking results demonstrate that compound 5a can interact with the tubulin colchicine binding site and generate multiple types of interactions. These results suggested that compound 5a has anticancer effects and significantly reverses cervical cancer resistance to cisplatin, which may be related to its inhibition of microtubule and P-glycoprotein (P-gp) activity.

2.
BMC Med ; 22(1): 148, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38561738

RESUMO

BACKGROUND: Indobufen is widely used in patients with aspirin intolerance in East Asia. The OPTION trial launched by our cardiac center examined the performance of indobufen based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, the vast majority of patients with acute coronary syndrome (ACS) and aspirin intolerance were excluded. We aimed to explore this question in a real-world population. METHODS: Patients enrolled in the ASPIRATION registry were grouped according to the DAPT strategy that they received after PCI. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. Propensity score matching (PSM) was adopted for confounder adjustment. RESULTS: A total of 7135 patients were reviewed. After one-year follow-up, the indobufen group was associated with the same risk of MACCE versus the aspirin group after PSM (6.5% vs. 6.5%, hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.65 to 1.52, P = 0.978). However, BARC type 2, 3, or 5 bleeding was significantly reduced (3.0% vs. 11.9%, HR = 0.24, 95% CI = 0.15 to 0.40, P < 0.001). These results were generally consistent across different subgroups including aspirin intolerance, except that indobufen appeared to increase the risk of MACCE in patients with ACS. CONCLUSIONS: Indobufen shared the same risk of MACCE but a lower risk of bleeding after PCI versus aspirin from a real-world perspective. Due to the observational nature of the current analysis, future studies are still warranted to further evaluate the efficacy of indobufen based DAPT, especially in patients with ACS. TRIAL REGISTRATION: Chinese Clinical Trial Register ( https://www.chictr.org.cn ); Number: ChiCTR2300067274.


Assuntos
Síndrome Coronariana Aguda , Isoindóis , Intervenção Coronária Percutânea , Fenilbutiratos , Humanos , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Aspirina/efeitos adversos , Quimioterapia Combinada , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/efeitos adversos , Sistema de Registros , Resultado do Tratamento
3.
Acta Biomater ; 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38561074

RESUMO

Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. SAH disrupts the blood‒brain barrier, leading to the release of iron ions from blood within the subarachnoid space, subsequently inducing neuronal ferroptosis. A recently discovered protein, known as ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10 by introducing the neuron-targeting peptide Tet1 onto the surface of liposomal CoQ10. Our objective was to determine whether this formulation could activate the FSP1 system and subsequently inhibit neuronal ferroptosis. Our findings revealed that neuron-targeted liposomal CoQ10 effectively localized to neurons at the lesion site after SAH. Furthermore, it facilitated the upregulation of FSP1, reduced the accumulation of malondialdehyde and reactive oxygen species, inhibited neuronal ferroptosis, and exerted neuroprotective effects both in vitro and in vivo. Our study provides evidence that supplementation with CoQ10 can effectively activate the FSP1 system. Additionally, we developed a neuron-targeted liposomal CoQ10 formulation that can be selectively delivered to neurons at the site of SAH. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH. STATEMENT OF SIGNIFICANCE: Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. Ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10. We find that it effectively localized to neurons at the lesion site after SAH and activated the FSP1/CoQ10 system. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH and other central nervous system diseases characterized by disruption of the blood-brain barrier.

4.
Psychol Res Behav Manag ; 17: 853-865, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444720

RESUMO

Background: Maternal anxiety or depression in the perinatal period has a high prevalence. The negative emotion during the puerpera is unfavorable to the process of childbirth and also affects the recovery and the quality of life in postpartum patients significantly. The present study aimed to elucidate the risk factors of negative emotion in perinatal women and its influence on prognosis to provide a reference for improving maternal prognosis. Methods: Initially, 350 expectant mothers were randomly enrolled in the present study between August 2021 and August 2022. Among these, after applying the established inclusion and exclusion criteria, 314 patients were eventually selected. The independent risk factors of negative emotion and poor prognosis were analyzed through binary logistics regression and multiple linear regression. Follow-up was conducted via telephone, email, and a follow-up visit one month after discharge. Results: Among the included patients, 18 (5.7%) had prenatal anxiety, 16 (5.1%) had prenatal depression, 31 (9.9%) had postnatal anxiety, and 28 (8.9%) had postnatal depression. Perinatal negative emotional risk factors include age, marital relationship, regular prenatal examination, E2 level, 5-HT level before and after delivery, family monthly income, neonatal health, breastfeeding time, intrapartum hemorrhage, constipation and other complications. The development of postpartum negative emotions is a risk factor for maternal prognosis. Conclusion: The results showed that the risk factors of perinatal depression and anxiety were complex. In order to improve the quality of life of pregnant women, maintain their long-term emotional stability, and promote their postpartum recovery, it may be considered to promote the use of screening tools to identify women at risk of anxiety and depression before and after delivery, and timely psychological counseling for patients with high risk factors to promote their mental health.

5.
Aesthetic Plast Surg ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448603

RESUMO

BACKGROUND: Thread-lifting (TL) is a minimally-invasive technique for facial rejuvenation, whereas liposuction is commonly used for facial contouring. This retrospective cohort study aims to introduce and evaluate a novel technique that combines liposuction and thread-lifting for mid-lower facial rejuvenation. METHODS: Consecutive patients who underwent TL for mid-lower facial rejuvenation from May 2016 to May 2021 were divided into thread-lifting group (TL group) or thread-lifting plus liposuction group (TLL group) according to whether liposuction was performed adjunctively. The co-primary outcomes were the changes between the preoperative and 6-month postoperative Wrinkle Severity Rating Scale (WSRS) and Facial Aging Evaluation Scale (FAES). RESULTS: A total of 185 patients (184 females) with an average age of 34.5±5.5 years were included. There were no significant differences in patients' age, number of threads, and preoperative WSRS and FAES between the two groups. The TLL group (n = 128) had significantly lower postoperative WSRS (1.5±0.6 vs. 1.8±0.8, p<0.001) and FAES (2.5±1.4 vs. 3.8±2.1, p<0.001) than the TL group (n = 57). The decrease in WSRS (0.8±0.6 vs. 0.2±0.7, p<0.001) and FAES (2.7±1.3 vs. 1.6±1.6, p<0.001) were greater in the TLL group. Only 3.8% patients experienced slight side effects and totally recovered. CONCLUSIONS: The combination of TL and liposuction is an effective and safe technique for simultaneous contour improvement and facial rejuvenation in middle-aged East Asian females. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266 .

6.
Front Pharmacol ; 15: 1345779, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38425646

RESUMO

A wound takes a long time to heal and involves several steps. Following tissue injury, inflammation is the primary cause of tissue regeneration and repair processes. As a result, the pathophysiological processes involving skin damage, healing, and remodeling depend critically on the control of inflammation. The fact that it is a feasible target for improving the prognosis of wound healing has lately become clear. Mesenchymal stem cells (MSCs) are an innovative and effective therapeutic option for wound healing due to their immunomodulatory and paracrine properties. By controlling the inflammatory milieu of wounds through immunomodulation, transplanted MSCs have been shown to speed up the healing process. In addition to other immunomodulatory mechanisms, including handling neutrophil activity and modifying macrophage polarization, there may be modifications to the activation of T cells, natural killer (NK) cells, and dendritic cells (DCs). Furthermore, several studies have shown that pretreating MSCs improves their ability to modulate immunity. In this review, we summarize the existing knowledge about how MSCs influence local inflammation in wounds by influencing immunity to facilitate the healing process. We also provide an overview of MSCs optimizing techniques when used to treat wounds.

7.
ACS Appl Mater Interfaces ; 16(13): 16482-16493, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38506366

RESUMO

The interfacial pyro-phototronic effect (IPPE) presents a novel approach for improving the performance of self-powered photodetectors (PDs) based on metal halide perovskites (MHPs). The interfacial contact conditions within the Schottky junctions are crucial in facilitating the IPPE phenomenon. However, the fabrication of an ideal Schottky junction utilizing MHPs is a challenging endeavor. In this study, we present a surface passivation method aimed at enhancing the performance of self-powered photodetectors based on inverted planar perovskite structures in micro- and nanoscale metal-halide perovskite SCs. Our findings demonstrate that the incorporation of a lead halide salt with a benzene ring moiety for surface passivation leads to a substantial improvement in photoresponses by means of the IPPE. Conversely, the inclusion of an alkane chain in the salt impedes the IPPE. The underlying mechanism can be elucidated through an examination of the band structure, particularly the work function (WF) modulated by surface passivation. Consequently, this alteration affects the band bending and the built-in field (VBi) at the interface. This strategy presents a feasible and effective method for producing interfacial pyroelectricity in MHPs, thus facilitating its potential application in practical contexts such as energy conversion and infrared sensors.

8.
IEEE Trans Image Process ; 33: 2665-2675, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38530731

RESUMO

Previous monocular 3D detection works focus on the single frame input in both training and inference. In real-world applications, temporal and motion information naturally exists in monocular video. It is valuable for 3D detection but under-explored in monocular works. In this paper, we propose a straightforward and effective method for temporal feature fusion, which exhibits low computation cost and excellent transferability, making it conveniently applicable to various monocular models. Specifically, with the help of optical flow, we transform the backbone features produced by prior frames and fuse them into the current frame. We introduce the scene feature propagating mechanism, which accumulates history scene features without extra time-consuming. In this process, occluded areas are removed via forward-backward scene consistency. Our method naturally introduces valuable temporal features, facilitating 3D reasoning in monocular 3D detection. Furthermore, accumulated history scene features via scene propagating mitigate heavy computation overheads for video processing. Experiments are conducted on variant baselines, which demonstrate that the proposed method is model-agonistic and can bring significant improvement to multiple types of single-frame methods.

9.
Medicine (Baltimore) ; 103(11): e37508, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489697

RESUMO

To analyze the effects of high ligation plus endovenous laser therapy on intraoperative blood loss, postoperative visual analogue scale (VAS) score, and complications in patients with varicosis of great saphenous vein and type 2 diabetes. About 61 patients with varicosis of great saphenous vein and type 2 diabetes treated at our hospital were included. About 32 patients (37 affected limbs) receiving conventional surgery were included in control group, while 29 patients (34 affected limbs) receiving high ligation plus endovenous laser therapy were included in study group. The intraoperative blood loss, operation time, length of postoperative hospital stay, postoperative VAS scores, blood glucose levels, Venous Clinical Severity Score (VCSS), and incidence of complications were compared between the two groups. Compared with the control group, there were less intraoperative blood loss (P < .05), shorter operation time (P < .05), and shorter length of postoperative hospital stay in the study group (P < .05). Besides, there was also lower VAS scores at different time points after surgery in the study group than in the control group (P < .05). Blood glucose levels were decreased in both groups after surgery (P < .05). Moreover, VCSS was decreased in either group at 3 months after surgery (P < .05). Blood glucose levels of patients in the study group were lower than those of the control group after surgery (P < .05). The VCSS was also lower in the study group at 3 months after surgery than in the control group (P < .05). High ligation with endovenous laser therapy for varicosis of great saphenous vein in patients with type 2 diabetes was safe and feasible.


Assuntos
Diabetes Mellitus Tipo 2 , Terapia a Laser , Varizes , Humanos , Varizes/terapia , Veia Safena/cirurgia , Diabetes Mellitus Tipo 2/etiologia , Perda Sanguínea Cirúrgica , Glicemia , Terapia a Laser/efeitos adversos , Resultado do Tratamento , Ligadura/efeitos adversos
10.
Cancer Med ; 13(5): e7015, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38491808

RESUMO

BACKGROUND: Gastric cardia adenocarcinoma (GCA) is classified as Siewert type II adenocarcinoma at the esophagogastric junction in Western countries. The majority of GCA patients do not exhibit early warning symptoms, leading to over 90% of diagnoses at an advanced stage, resulting in a grim prognosis, with less than a 20% 5-year survival rate. METHOD: Metabolic features of 276 GCA and 588 healthy controls were characterized through a widely-targeted metabolomics by UPLC-MS/MS analysis. This study encompasses a joint pathway analysis utilizing identified metabolites, survival analysis in both early and advanced stages, as well as high and negative and low expression of HER2 immunohistochemistry staining. Machine learning techniques and Cox regression models were employed to construct a diagnostic panel. RESULTS: A total of 25 differential metabolites were consistently identified in both discovery and validation sets based on criteria of p < 0.05, (VIP) ≥ 1, and FC ≥ 2 or FC ≤ 0.5. Early-stage GCA patients exhibited a more favorable prognosis compared to those in advanced stages. HER2 overexpression was associated with a more positive outcome compared to the negative and low expression groups. Metabolite panel demonstrated a robust diagnostic performance with AUC of 0.869 in discovery set and 0.900 in validation set. CONCLUSIONS: A total of 25 common and stable differential metabolites may hold promise as liquid non-invasive indicators for GCA diagnosis. HER2 may function as a tumor suppressor gene in GCA, as its overexpression is associated with improved survival. The downregulation of bile acid metabolism in GCA may offer valuable theoretical insights and innovative approaches for precision-targeted treatments in GCA patients.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Cárdia/patologia , Cromatografia Líquida , Espectrometria de Massas em Tandem , Neoplasias Gástricas/patologia , Adenocarcinoma/patologia , Biomarcadores
11.
Plant Physiol ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38506490

RESUMO

Iron (Fe) distribution and reutilization are crucial for maintaining Fe homeostasis in plants. Here, we demonstrate that the tomato (Solanum lycopersicum) Colorless non-ripening (Cnr) epimutant exhibits increased Fe retention in cell wall pectin due to an increase in pectin methylesterase (PME) activity. This ultimately leads to Fe deficiency responses even under Fe-sufficient conditions when compared to the wild type (WT). Whole-genome bisulfite sequencing revealed that modifications to cell wall-related genes, especially CG hypermethylation in the intron region of PECTIN METHYLESTERASE53 (SlPME53), are involved in the Cnr response to Fe deficiency. When this intron hypermethylation of SlPME53 was artificially induced in WT, we found that elevated SlPME53 expression was accompanied by increased PME activity and increased pectin-Fe retention. The manipulation of SlPME53, either through overexpression in WT or knockdown in Cnr, influenced levels of pectin methylesterification and accumulation of apoplast Fe in roots. Moreover, CG hypermethylation mediated by METHYLTRANSFERASE1 (SlMET1) increased SlPME53 transcript abundance, resulting in greater PME activity and higher Fe retention in cell wall pectin. Therefore, we conclude that the Cnr mutation epigenetically modulates SlPME53 expression by SlMET1-mediated CG hypermethylation, and thus the capacity of the apoplastic Fe pool, creating opportunities for genetic improvement of crop mineral nutrition.

12.
BMC Gastroenterol ; 24(1): 117, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515017

RESUMO

OBJECTIVE: To determine the high-efficiency ancillary features (AFs) screened from LR-3/4 lesions and the HCC/non-HCC group and the diagnostic performance of LR3/4 observations. MATERIALS AND METHODS: We retrospectively analyzed a total of 460 patients (with 473 nodules) classified into LR-3-LR-5 categories, including 311 cases of hepatocellular carcinoma (HCC), 6 cases of non-HCC malignant tumors, and 156 cases of benign lesions. Two faculty abdominal radiologists with experience in hepatic imaging reviewed and recorded the major features (MFs) and AFs of the Liver Imaging Reporting and Data System (LI-RADS). The frequency of the features and diagnostic performance were calculated with a logistic regression model. After applying the above AFs to LR-3/LR-4 observations, the sensitivity and specificity for HCC were compared. RESULTS: The average age of all patients was 54.24 ± 11.32 years, and the biochemical indicators ALT (P = 0.044), TBIL (P = 0.000), PLT (P = 0.004), AFP (P = 0.000) and Child‒Pugh class were significantly higher in the HCC group. MFs, mild-moderate T2 hyperintensity, restricted diffusion and AFs favoring HCC in addition to nodule-in-nodule appearance were common in the HCC group and LR-5 category. AFs screened from the HCC/non-HCC group (AF-HCC) were mild-moderate T2 hyperintensity, restricted diffusion, TP hypointensity, marked T2 hyperintensity and HBP isointensity (P = 0.005, < 0.001, = 0. 032, p < 0.001, = 0.013), and the AFs screened from LR-3/4 lesions (AF-LR) were restricted diffusion, mosaic architecture, fat in mass, marked T2 hyperintensity and HBP isointensity (P < 0.001, = 0.020, = 0.036, < 0.001, = 0.016), which were not exactly the same. After applying AF-HCC and AF-LR to LR-3 and LR-4 observations in HCC group and Non-HCC group, After the above grades changed, the diagnostic sensitivity for HCC were 84.96% using AF-HCC and 85.71% using AF-LR, the specificity were 89.26% using AF-HCC and 90.60% using AF-LR, which made a significant difference (P = 0.000). And the kappa value for the two methods of AF-HCC and AF-LR were 0.695, reaching a substantial agreement. CONCLUSION: When adjusting for LR-3/LR-4 lesions, the screened AFs with high diagnostic ability can be used to optimize LI-RADS v2018; among them, AF-LR is recommended for better diagnostic capabilities.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Estudos Retrospectivos , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética/métodos , Sensibilidade e Especificidade , Meios de Contraste
13.
Infect Drug Resist ; 17: 963-967, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495624

RESUMO

Background: Rickettsia japonica infection is a rare disease, it is rare to report critical and severe case caused by this disease in Zhejiang Province, China. Patient Concerns: We report a patient who initially sought medical attention due to fever and developed coma and convulsions during treatment. The patient did not develop typical eschar and rash. Eventually, the patient needed to be treated in the intensive care unit due to acute respiratory failure. Diagnoses: The patient was diagnosed with Rickettsia japonica bloodstream infection by metagenomic next-generation sequencing (mNGS). Outcomes: Due to the critical illness, the patient was transferred to the intensive care unit, received doxycycline and other treatments, and rapidly recovered and discharged. Conclusion: The patient developed a critical illness after being infected with Rickettsia, when the medical history is unclear and clinical symptoms and signs are atypical, it is necessary to use mNGS examination for diagnosis.

14.
ACS Omega ; 9(10): 11356-11365, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38496926

RESUMO

An efficient protocol for photocatalytic degradation of organic dyes and antibiotics has been successfully established via MOF-derived (MOF = metal-organic framework) Ni, Co-embedded N-doped bimetallic porous carbon nanocomposites (NiCo/NC). Such a NiCo/NC nanocomposite features well-distributed structures, suitable specific surface areas, and more active sites determined by various characterization analyses. The catalyst exhibits higher photocatalytic performance and stability toward the liquid-phase degradation of methylene blue (MB) under visible light irradiation for 60 min, after the adsorption-desorption equilibrium and the thorough degradation into H2O and CO2. Radical quenching experiments further confirmed the dominant effect of electron holes h+ and superoxide radical anions ·O2- for the MB photodegradation process. NiCo/NC was also appropriate for the degradation of Rhodamine B, methyl orange, tetracycline hydrochloride, and norfloxacin. Moreover, NiCo/NC is robust, and its photocatalytic activity is basically maintained after 8 cycles. This work is expected to provide additional information for the design of MOF-derived carbon material with more excellent properties and lay the foundation for further industrial applications.

15.
Plants (Basel) ; 13(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38475589

RESUMO

RNAs play important roles in regulating biological growth and development. Advancements in RNA-imaging techniques are expanding our understanding of their function. Several common RNA-labeling methods in plants have pros and cons. Simultaneously, plants' spontaneously fluorescent substances interfere with the effectiveness of RNA bioimaging. New technologies need to be introduced into plant RNA luminescence. Aggregation-induced emission luminogens (AIEgens), due to their luminescent properties, tunable molecular size, high fluorescence intensity, good photostability, and low cell toxicity, have been widely applied in the animal and medical fields. The application of this technology in plants is still at an early stage. The development of AIEgens provides more options for RNA labeling. Click chemistry provides ideas for modifying AIEgens into RNA molecules. The CRISPR/Cas13a-mediated targeting system provides a guarantee of precise RNA modification. The liquid-liquid phase separation in plant cells creates conditions for the enrichment and luminescence of AIEgens. The only thing that needs to be looked for is a specific enzyme that uses AIEgens as a substrate and modifies AIEgens onto target RNA via a click chemical reaction. With the development and progress of artificial intelligence and synthetic biology, it may soon be possible to artificially synthesize or discover such an enzyme.

16.
Heliyon ; 10(6): e27939, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38509994

RESUMO

Objective: Fibroblast growth factor 23 (FGF23) has been recognized as an important biomarker of cardiovascular disease and is closely related to inflammation over the past decade. This study aimed to assess the relationship between FGF23 and myocardial injury in patients with sepsis. Methods: We sequentially measured serum FGF23, Klotho, biomarkers of inflammation (CRP, IL-6 and WBC), myocardial injury (cTnI and N-terminal B-type natriuretic peptide) and sepsis (procalcitonin) at peak of intercurrent septic shock and after complete resolution or before death in a series of 29 patients with septic shock. 29 healthy adults without infections were used as controls. Results: There was a difference in serum FGF23 level between patients with septic shock and healthy adults (p < 0.0001), and the peak level of FGF23 in septic shock in the survivor group was higher than that after complete remission (p < 0.0001). No statistical difference was found in the level of FGF23 before and after treatment in the death group (p = 0.0947). At the peak of septic shock, FGF23 was significantly correlated with inflammatory markers, CRP (r = 0.8063, p < 0.0001), PCT (r = 0.6091, p = 0.0005) and WBC (r = 0.8312, p < 0.0001), while the correlation with IL-6 was not statistically significant (r = 0.0098, p = 0.9598). At the same time, it was found that FGF23 was significantly correlated with myocardial injury markers, cTNI (r = 0.8475, p < 0.0001) and NTproBNP (r = 0.8505, p < 0.0001). Nevertheless, FGF23 and klotho are not correlated (r = 0.2609, p = 0.1717). Conclusion: In conclusion, in patients with septic shock and myocardial injury, the exacerbation of inflammation in the septic process was accompanied by a abnormal increase of circulating FGF23 level. FGF23 also subsided after the improvement of inflammation, and the opposite was true for patients who did not survive. The up-regulation of FGF23 may be involved in the response of patients to septic shocks, and it is also speculated that FGF23 is involved in the myocardial injury of septic shock.

17.
World J Clin Cases ; 12(7): 1215-1226, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38524522

RESUMO

BACKGROUND: Although the etiology of nonalcoholic fatty liver disease (NAFLD) has not been thoroughly understood, the emerging roles of anthropometric indicators in assessing and predicting the risk of NAFLD have been highlighted by accumulating evidence. AIM: To evaluate the causal relationships between five anthropometric indicators and NAFLD employing Mendelian randomization (MR) design. METHODS: The Anthropometric Consortium provided genetic exposure data for five anthropometric indicators, including hip circumference (HC), waist circumference (WC), waist-to-hip ratio (WHR), body mass index (BMI), and body fat percentage (BF). Genetic outcome data for NAFLD were obtained from the United Kingdom Biobank and FinnGen Consortium. Genome-wide significant single nucleotide polymorphisms were chosen as instrumental variables. Univariable MR (UVMR) and multivariable MR (MVMR) designs with analytical approaches, including inverse variance weighted (IVW), MR-Egger, weighted median (WM), and weighted mode methods, were used to assess the causal relationships between anthropometric indicators and NAFLD. RESULTS: Causal relationships were revealed by UVMR, indicating that a higher risk of NAFLD was associated with a per-unit increase in WC [IVW: odds ratio (OR) = 2.67, 95%CI: 1.42-5.02, P = 2.25 × 10-3], and BF was causally associated with an increased risk of NAFLD (WM: OR = 2.23, 95%CI: 1.07-4.66, P = 0.033). The presence of causal effects of WC on the decreased risk of NAFLD was supported by MVMR after adjusting for BMI and smoking. However, no causal association between BF and NAFLD was observed. In addition, other causal relationships of HC, WHR (BMI adjusted), and BMI with the risk of NAFLD were not retained after FDR correction. CONCLUSION: This study establishes a causal relationship, indicating that an increase in WC is associated with a higher risk of NAFLD. This demonstrates that a suitable decrease in WC is advantageous for preventing NAFLD.

18.
J Pediatr Orthop ; 44(4): 236-243, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38298014

RESUMO

OBJECTIVE: Closed or open reduction and spica casting are common treatments for children aged 6 to 18 months, as well as infants aged 0 to 6 months whose harness treatment for developmental dysplasia of the hip (DDH) was unsuccessful. The study aimed to quantify the distance between the femoral head and the acetabulum after closed or open reduction and evaluate the dynamic docking progression of the femoral head using serial hip medical ultrasound. METHODS: We retrospectively reviewed the medical records and hip medial ultrasound images of a consecutive series of patients with DDH who underwent spica casting after reduction and compared images obtained immediately after reduction and at follow-up. The first cast (stage I) was maintained for 2 to 3 months and scheduled for outpatient repeat ultrasound in 4 to 8 weeks. Then the second cast was placed (stage II), lasting for another 2 to 3 months. The triradiate cartilage-femoral head distance (TFD) was measured in the acetabulum coronal mid-sectional plane. The Wilcoxon signed-rank test was used to compare the TFD values. RESULTS: This study included 49 patients. All patients underwent hip medial ultrasound 0 to 3 days after stage I (time 1) and 4 to 8 weeks (time 2) postoperatively, with 24 patients reviewed again 0 to 7 days after stage II. The TFD values in time 1 and time 2 were 6.0 (5.0, 9.0) mm and 5.0 (3.6, 7.0) mm, respectively. There was a statistically significant difference between times 1 and 2 regarding TFD values in 49 close-reduction hips (6.0 vs 5.0 mm, P < 0.001). Similar findings were also observed in 13 open-reduction hips (6.0 vs 5.0 mm, P = 0.023). CONCLUSIONS: Hip medial ultrasonography during the period of cast immobilization after reduction in children with DDH can objectively and quantitatively show the dynamic change of the distance between the femoral head and the acetabulum, and can be used to assess reduction of the hip and progression of femoral head docking. LEVEL OF EVIDENCE: Level II-prognostic study.


Assuntos
Displasia do Desenvolvimento do Quadril , Luxação Congênita de Quadril , Lactente , Criança , Humanos , Luxação Congênita de Quadril/terapia , Luxação Congênita de Quadril/cirurgia , Seguimentos , Resultado do Tratamento , Estudos Retrospectivos , Displasia do Desenvolvimento do Quadril/diagnóstico por imagem , Displasia do Desenvolvimento do Quadril/terapia , Ultrassonografia
19.
Mol Med ; 30(1): 29, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395744

RESUMO

BACKGROUND: The escalating challenge of Carbapenem-resistant Klebsiella pneumoniae (CRKP) in hospital-acquired pneumonia (HAP) is closely linked to the blaNDM-1 gene. This study explores the regulatory mechanisms of blaNDM-1 expression and aims to enhance antibacterial tactics to counteract the spread and infection of resistant bacteria. METHODS: KP and CRKP strains were isolated from HAP patients' blood samples. Transcriptomic sequencing (RNA-seq) identified significant upregulation of blaNDM-1 gene expression in CRKP strains. Bioinformatics analysis revealed blaNDM-1 gene involvement in beta-lactam resistance pathways. CRISPR-Cas9 was used to delete the blaNDM-1 gene, restoring sensitivity. In vitro and in vivo experiments demonstrated enhanced efficacy with Imipenem and Thanatin or Subatan combination therapy. RESULTS: KP and CRKP strains were isolated with significant upregulation of blaNDM-1 in CRKP strains identified by RNA-seq. The Beta-lactam resistance pathway was implicated in bioinformatics analysis. Knockout of blaNDM-1 reinstated sensitivity in CRKP strains. Further, co-treatment with Imipenem, Thanatin, or Subactam markedly improved antimicrobial effectiveness. CONCLUSION: Silencing blaNDM-1 in CRKP strains from HAP patients weakens their Carbapenem resistance and optimizes antibacterial strategies. These results provide new theoretical insights and practical methods for treating resistant bacterial infections.


Assuntos
Infecções por Klebsiella , Pneumonia , Humanos , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Klebsiella pneumoniae/genética , Farmacorresistência Bacteriana/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Imipenem , Hospitais , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/genética , Infecções por Klebsiella/microbiologia
20.
bioRxiv ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38405790

RESUMO

Mitochondria-ER contact sites (MERCS) serve as hotspots for important cellular processes, including calcium homeostasis, phospholipid homeostasis, mitochondria dynamics, and mitochondrial quality control. MERCS reporters based on complementation of GFP fragments have been designed to visualize MERCS in real-time, but we find that they do not accurately respond to changes in MERCS content. Here, we utilize split LacZ complementing fragments to develop the first MERCS reporter system (termed SpLacZ-MERCS) that continuously integrates the MERCS information within a cell and generates a fluorescent output. Our system exhibits good organelle targeting, no artifactual tethering, and effective, dynamic tracking of the MERCS level in single cells. The SpLacZ-MERCS reporter was validated by drug treatments and genetic perturbations known to affect mitochondria-ER contacts. The signal-integrating nature of SpLacZ-MERCS may enable systematic identification of genes and drugs that regulate mitochondria-ER interactions. Our successful application of the split LacZ complementation strategy to study MERCS may be extended to study other forms of inter-organellar crosstalk.

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