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1.
Ital J Pediatr ; 50(1): 77, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641843

RESUMO

BACKGROUND: Epilepsy is a chronic neurological disorder that is more likely to be diagnosed in children. The main treatment involves long-term use of anti-epileptic drugs and above all, home care is of great importance. As there has not been a widely accepted home care protocols, simulating a home care environment is necessary for caregivers to develop skills of proper home care. This study aims to evaluate the effectiveness of a simulation training of family management style (STOFMS) for parents of children with epilepsy in China. METHODS: A randomized controlled trial was conducted on 463 children with epilepsy and their families. They were recruited from March 2020 to November 2022 and randomly assigned to the STOFMS group or the conventional group in a 1:1 ratio. Scores of family management measures, 8-item of Morisky Medication Adherence and epilepsy clinical symptom of both groups were collected at three points of time: within 24 h after admission (T0), 3 months after discharge (T1), and 6 months after discharge (T2). Changes due to intervention were compared across groups by repeated-measures ANOVA. The study report followed the CONSORT 2010 checklist. RESULTS: There were statistically significant differences between the two groups at T2. A considerable increase over the baseline was observed in the total management level score and subscale scores in the STOFMS group at T1, compared with essentially no change in the control group. In terms of medication adherence, the STOFMS group performance improved greatly at T1 and T2 compared with the control group. The same result was also found in clinical efficacy at T2 (p < 0.05). CONCLUSION: STOFMS is an effective intervention to improve family management level, treatment adherence and clinical efficacy for children with epilepsy. TRIAL REGISTRATION: The registration number is ChiCTR2200065128. Registered at 18 October 2022, http://www.medresman.org.cn.


Assuntos
Epilepsia , Serviços de Assistência Domiciliar , Treinamento por Simulação , Criança , Humanos , Pais/educação , Epilepsia/terapia , Cuidadores
2.
Aging (Albany NY) ; 16(7): 6588-6612, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38604156

RESUMO

BACKGROUND: Liver progenitor cells (LPCs) are a subpopulation of cells that contribute to liver regeneration, fibrosis and liver cancer initiation under different circumstances. RESULTS: By performing adenoviral-mediated transfection, CCK-8 analyses, F-actin staining, transwell analyses, luciferase reporter analyses and Western blotting, we observed that TGF-ß promoted cytostasis and partial epithelial-mesenchymal transition (EMT) in LPCs. In addition, we confirmed that TGF-ß activated the Smad and MAPK pathways, including the Erk, JNK and p38 MAPK signaling pathways, and revealed that TGFß-Smad signaling induced growth inhibition and partial EMT, whereas TGFß-MAPK signaling had the opposite effects on LPCs. We further found that the activity of Smad and MAPK signaling downstream of TGF-ß was mutually restricted in LPCs. Mechanistically, we found that TGF-ß activated Smad signaling through serine phosphorylation of both the C-terminal and linker regions of Smad2 and 3 in LPCs. Additionally, TGFß-MAPK signaling inhibited the phosphorylation of Smad3 but not Smad2 at the C-terminus, and it reinforced the linker phosphorylation of Smad3 at T179 and S213. We then found that overexpression of mutated Smad3 at linker phosphorylation sites intensifies TGF-ß-induced cytostasis and EMT, mimicking the effects of MAPK inhibition in LPCs, whereas mutation of Smad3 at the C-terminus caused LPCs to blunt TGF-ß-induced cytostasis and partial EMT. CONCLUSION: These results suggested that TGF-ß downstream of Smad3 and MAPK signaling were mutually antagonistic in regulating the viability and partial EMT of LPCs. This antagonism may help LPCs overcome the cytostatic effect of TGF-ß under fibrotic conditions and maintain partial EMT and progenitor phenotypes.


Assuntos
Transição Epitelial-Mesenquimal , Fígado , Sistema de Sinalização das MAP Quinases , Proteína Smad3 , Células-Tronco , Fator de Crescimento Transformador beta , Proteína Smad3/metabolismo , Células-Tronco/metabolismo , Animais , Fator de Crescimento Transformador beta/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Fígado/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Fosforilação , Camundongos , Transdução de Sinais
3.
Cell Rep ; 43(4): 114098, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38625793

RESUMO

Developing an effective mRNA therapeutic often requires maximizing protein output per delivered mRNA molecule. We previously found that coding sequence (CDS) design can substantially affect protein output, with mRNA variants containing more optimal codons and higher secondary structure yielding the highest protein outputs due to their slow rates of mRNA decay. Here, we demonstrate that CDS-dependent differences in translation initiation and elongation rates lead to differences in translation- and deadenylation-dependent mRNA decay rates, thus explaining the effect of CDS on mRNA half-life. Surprisingly, the most stable and highest-expressing mRNAs in our test set have modest initiation/elongation rates and ribosome loads, leading to minimal translation-dependent mRNA decay. These findings are of potential interest for optimization of protein output from therapeutic mRNAs, which may be achieved by attenuating rather than maximizing ribosome load.


Assuntos
Biossíntese de Proteínas , Estabilidade de RNA , RNA Mensageiro , Ribossomos , Ribossomos/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Humanos
4.
Phys Chem Chem Phys ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639877

RESUMO

Intrinsic half-metallic nanomaterials with 100% spin polarization are highly demanded for next-generation spintronic devices. Here, by using first-principles calculations, we have designed a class of new two-dimensional (2D) p-type half-metals, MSi2N4 (M = Al, Ga, In and Tl), which show high mechanical, thermal and dynamic stabilities. MSi2N4 not only have ultrawide electronic bandgaps for spin-up channels in the range of 4.05 to 6.82 eV but also have large half-metallic gaps in the range of 0.75 to 1.47 eV, which are large enough to prevent the spin-flip transition. The calculated magnetic moment is 1 µB per cell, resulting from polarized N1-px/py orbitals. Moreover, MSi2N4 possess robust long-range ferromagnetic orderings with Curie temperatures in the range of 35-140 K, originating from the interplay of N1-M-N1 superexchange interactions. Furthermore, spin dependent electronic transport calculations reveal 100% spin polarization. Our results highlight new promising 2D ferromagnetic half-metals toward future spintronic applications.

5.
bioRxiv ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38559216

RESUMO

The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted a comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization resistance, infectivity, antigenicity, cell-cell fusion, and spike processing. Neutralizing antibody (nAb) titers were assessed in diverse cohorts, including individuals who received a bivalent mRNA vaccine booster, patients infected during the BA.2.86/JN.1-wave, and hamsters vaccinated with XBB.1.5-monovalent vaccine. We found that BA.2.87.1 shows much less nAb escape from WT-BA.4/5 bivalent mRNA vaccination and JN.1-wave breakthrough infection sera compared to JN.1 and XBB.1.5. Interestingly. BA.2.87.1 is more resistant to neutralization by XBB.15-monovalent-vaccinated hamster sera than BA.2.86/JN.1 and XBB.1.5, but efficiently neutralized by a class III monoclonal antibody S309, which largely fails to neutralize BA.2.86/JN.1. Importantly, BA.2.87.1 exhibits higher levels of infectivity, cell-cell fusion activity, and furin cleavage efficiency than BA.2.86/JN.1. Antigenically, we found that BA.2.87.1 is closer to the ancestral BA.2 compared to other recently emerged Omicron subvariants including BA.2.86/JN.1 and XBB.1.5. Altogether, these results highlight immune escape properties as well as biology of new variants and underscore the importance of continuous surveillance and informed decision-making in the development of effective vaccines.

6.
mBio ; : e0075124, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38591890

RESUMO

The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted a comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization resistance, infectivity, antigenicity, cell-cell fusion, and spike processing. Neutralizing antibody (nAb) titers were assessed in diverse cohorts, including individuals who received a bivalent mRNA vaccine booster, patients infected during the BA.2.86/JN.1-wave, and hamsters vaccinated with XBB.1.5-monovalent vaccine. We found that BA.2.87.1 shows much less nAb escape from WT-BA.4/5 bivalent mRNA vaccination and JN.1-wave breakthrough infection sera compared to JN.1 and XBB.1.5. Interestingly, BA.2.87.1 is more resistant to neutralization by XBB.1.5-monovalent-vaccinated hamster sera than BA.2.86/JN.1 and XBB.1.5, but efficiently neutralized by a class III monoclonal antibody S309, which largely fails to neutralize BA.2.86/JN.1. Importantly, BA.2.87.1 exhibits higher levels of infectivity, cell-cell fusion activity, and furin cleavage efficiency than BA.2.86/JN.1. Antigenically, we found that BA.2.87.1 is closer to the ancestral BA.2 compared to other recently emerged Omicron subvariants including BA.2.86/JN.1 and XBB.1.5. Altogether, these results highlight immune escape properties as well as biology of new variants and underscore the importance of continuous surveillance and informed decision-making in the development of effective vaccines. IMPORTANCE: This study investigates the recently emerged SARS-CoV-2 variants, BA.2.87.1 and JN.1, in comparison to earlier variants and the parental D614G. Varied infectivity and cell-cell fusion activity among these variants suggest potential disparities in their ability to infect target cells and possibly pathogenesis. BA.2.87.1 exhibits lower nAb escape from bivalent mRNA vaccinee and BA.2.86/JN.1-infected sera than JN.1 but is relatively resistance to XBB.1.5-vaccinated hamster sera, revealing distinct properties in immune reason and underscoring the significance of continuing surveillance of variants and reformulation of vaccines. Antigenic differences between BA.2.87.1 and other earlier variants yield critical information not only for antibody evasion but also for viral evolution. In conclusion, this study furnishes timely insights into the spike biology and immune escape of the emerging variants BA.2.87.1 and JN.1, thus guiding effective vaccine development and informing public health interventions.

7.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(3): 262-268, 2024 Mar 15.
Artigo em Chinês | MEDLINE | ID: mdl-38557378

RESUMO

OBJECTIVES: To investigate the factors influencing the occurrence of small for gestational age (SGA) at different degrees and provide a basis for early identification of severe SGA cases. METHODS: Neonatal and maternal prenatal information were retrospectively collected from January 2018 to December 2022 at Peking University People's Hospital. The neonates were divided into three groups: severe SGA group (birth weight below the 3rd percentile for gestational age and sex), mild SGA group (birth weight ≥3rd percentile and <10th percentile), and non-SGA group (birth weight ≥10th percentile). An ordered multinomial logistic regression model was used to analyze the factors influencing the occurrence of SGA at different degrees. RESULTS: A total of 14 821 neonates were included, including 258 cases (1.74%) in the severe SGA group, 902 cases (6.09%) in the mild SGA group, and 13 661 cases (92.17%) in the non-SGA group. The proportions of preterm births and stillbirths were higher in the severe SGA group compared to the mild SGA and non-SGA groups (P<0.0125). The proportion of neonatal asphyxia was higher in both the severe SGA and mild SGA groups compared to the non-SGA group (P<0.0125). Ordered multinomial logistic regression analysis showed that maternal pre-pregnancy underweight (OR=1.838), maternal pre-pregnancy obesity (OR=3.024), in vitro fertilization-embryo transfer (OR=2.649), preeclampsia (OR=1.743), connective tissue disease during pregnancy (OR=1.795), nuchal cord (OR=1.213), oligohydramnios (OR=1.848), and intrauterine growth restriction (OR=27.691) were all associated with a higher risk of severe SGA (P<0.05). Maternal parity as a multipara (OR=0.457) was associated with a lower likelihood of severe SGA (P<0.05). CONCLUSIONS: Maternal pre-pregnancy underweight, maternal pre-pregnancy obesity, in vitro fertilization-embryo transfer, preeclampsia, connective tissue disease during pregnancy, oligohydramnios, nuchal cord, and intrauterine growth restriction are closely related to the occurrence of more severe SGA. Maternal parity as a multipara acts as a protective factor against the occurrence of severe SGA.


Assuntos
Doenças do Tecido Conjuntivo , Cordão Nucal , Oligo-Hidrâmnio , Pré-Eclâmpsia , Gravidez , Recém-Nascido , Feminino , Humanos , Retardo do Crescimento Fetal , Peso ao Nascer , Idade Gestacional , Estudos Retrospectivos , Magreza , Recém-Nascido Pequeno para a Idade Gestacional , Obesidade
8.
Ann Surg ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557792

RESUMO

OBJECTIVE: To develop an artificial intelligence (AI) system for the early prediction of residual cancer burden (RCB) scores during neoadjuvant chemotherapy (NAC) in breast cancer. SUMMARY BACKGROUND DATA: RCB III indicates drug resistance in breast cancer, and early detection methods are lacking. METHODS: This study enrolled 1048 patients with breast cancer from four institutions, who were all receiving NAC. Magnetic resonance images were collected at the pre- and mid-NAC stages, and radiomics and deep learning features were extracted. A multitask AI system was developed to classify patients into three groups (RCB 0-I, II, and III ) in the primary cohort (PC, n=335). Feature selection was conducted using the Mann-Whitney U- test, Spearman analysis, least absolute shrinkage and selection operator regression, and the Boruta algorithm. Single-modality models were developed followed by model integration. The AI system was validated in three external validation cohorts. (EVCs, n=713). RESULTS: Among the patients, 442 (42.18%) were RCB 0-I, 462 (44.08%) were RCB II and 144 (13.74%) were RCB III. Model-I achieved an area under the curve (AUC) of 0.975 in the PC and 0.923 in the EVCs for differentiating RCB III from RCB 0-II. Model-II distinguished RCB 0-I from RCB II-III, with an AUC of 0.976 in the PC and 0.910 in the EVCs. Subgroup analysis confirmed that the AI system was consistent across different clinical T stages and molecular subtypes. CONCLUSIONS: The multitask AI system offers a noninvasive tool for the early prediction of RCB scores in breast cancer, supporting clinical decision-making during NAC.

9.
Clin Cancer Res ; : OF1-OF10, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652038

RESUMO

PURPOSE: ARO-HIF2 is an siRNA drug designed to selectively target hypoxia-inducible factor-2α (HIF2α) interrupting downstream pro-oncogenic signaling in clear cell renal cell carcinoma (ccRCC). The aims of this Phase 1 study (AROHIF21001) were to evaluate safety, tolerability, pharmacokinetics, and establish a recommended Phase 2 dose. PATIENTS AND METHODS: Subjects with ccRCC and progressive disease after at least 2 prior therapies that included VEGF and immune checkpoint inhibitors were progressively enrolled into dose-escalation cohorts of ARO-HIF2 administered intravenously at 225, 525, or 1,050 mg weekly. RESULTS: Twenty-six subjects received ARO-HIF2. The most common treatment emergent adverse events (AE) irrespective of causality were fatigue (50.0%), dizziness (26.9%), dyspnea (23.1%), and nausea (23.1%). Four subjects (15.4%) had treatment-related serious AEs. AEs of special interest included neuropathy, hypoxia, and dyspnea. ARO-HIF2 was almost completely cleared from plasma circulation within 48 hours with minimal renal clearance. Reductions in HIF2α were observed between pre- and post-dosing tumor biopsies, but the magnitude was quite variable. The objective response rate was 7.7% and the disease control rate was 38.5%. Responses were accompanied by ARO-HIF2 uptake in tumor cells, HIF2α downregulation, as well as rapid suppression of tumor produced erythropoietin (EPO) in a patient with paraneoplastic polycythemia. CONCLUSIONS: ARO-HIF2 downregulated HIF2α in advanced ccRCC-inhibiting tumor growth in a subset of subjects. Further development was hampered by off-target neurotoxicity and low response rate. This study provides proof of concept that siRNA can target tumors in a specific manner.

10.
IEEE J Transl Eng Health Med ; 12: 401-412, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38606393

RESUMO

Osteoporosis is a prevalent chronic disease worldwide, particularly affecting the aging population. The gold standard diagnostic tool for osteoporosis is Dual-energy X-ray Absorptiometry (DXA). However, the expensive cost of the DXA machine and the need for skilled professionals to operate it restrict its accessibility to the general public. This paper builds upon previous research and proposes a novel approach for rapidly screening bone density. The method involves utilizing near-infrared light to capture local body information within the human body. Deep learning techniques are employed to analyze the obtained data and extract meaningful insights related to bone density. Our initial prediction, utilizing multi-linear regression, demonstrated a strong correlation (r = 0.98, p-value = 0.003**) with the measured Bone Mineral Density (BMD) obtained from Dual-energy X-ray Absorptiometry (DXA). This indicates a highly significant relationship between the predicted values and the actual BMD measurements. A deep learning-based algorithm is applied to analyze the underlying information further to predict bone density at the wrist, hip, and spine. The prediction of bone densities in the hip and spine holds significant importance due to their status as gold-standard sites for assessing an individual's bone density. Our prediction rate had an error margin below 10% for the wrist and below 20% for the hip and spine bone density.


Assuntos
Densidade Óssea , Osteoporose , Humanos , Idoso , Osteoporose/diagnóstico , Osso e Ossos , Absorciometria de Fóton/métodos , Coluna Vertebral
11.
Biomed Opt Express ; 15(4): 2343-2357, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38633066

RESUMO

In neurosurgery, accurately identifying brain tumor tissue is vital for reducing recurrence. Current imaging techniques have limitations, prompting the exploration of alternative methods. This study validated a binary hierarchical classification of brain tissues: normal tissue, primary central nervous system lymphoma (PCNSL), high-grade glioma (HGG), and low-grade glioma (LGG) using transfer learning. Tumor specimens were measured with optical coherence tomography (OCT), and a MobileNetV2 pre-trained model was employed for classification. Surgeons could optimize predictions based on experience. The model showed robust classification and promising clinical value. A dynamic t-SNE visualized its performance, offering a new approach to neurosurgical decision-making regarding brain tumors.

12.
World J Diabetes ; 15(3): 418-428, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38591072

RESUMO

BACKGROUND: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is rapidly increasing, currently affecting approximately 25% of the global population. Liver fibrosis represents a crucial stage in the development of MAFLD, with advanced liver fibrosis elevating the risks of cirrhosis and hepatocellular carcinoma. Simple serum markers are less effective in diagnosing liver fibrosis compared to more complex markers. However, imaging techniques like transient elastography face limitations in clinical application due to equipment and technical constraints. Consequently, it is imperative to identify a straightforward yet effective method for assessing MAFLD-associated liver fibrosis. AIM: To investigate the predictive value of angiopoietin-like protein 8 (ANGPTL8) in MAFLD and its progression. METHODS: We analyzed 160 patients who underwent abdominal ultrasonography in the Endocrinology Department, Xiaogan Central Hospital affiliated to Wuhan University of Science and Technology, during September 2021-July 2022. Using abdominal ultrasonography and MAFLD diagnostic criteria, among the 160 patients, 80 patients (50%) were diagnosed with MAFLD. The MAFLD group was divided into the liver fibrosis group (n = 23) and non-liver fibrosis group (n = 57) by using a cut-off fibrosis-4 index ≥ 1.45. Logistical regression was used to analyze the risk of MAFLD and the risk factors for its progression. Receiver operating characteristic curves were used to evaluate the predictive value of serum ANGPTL8 in MAFLD and its progression. RESULTS: Compared with non-MAFLD patients, MAFLD patients had higher serum ANGPTL8 and triglyceride-glucose (TyG) index (both P < 0.05). Serum ANGPTL8 (r = 0.576, P < 0.001) and TyG index (r = 0.473, P < 0.001) were positively correlated with MAFLD. Serum ANGPTL8 was a risk factor for MAFLD [odds ratio (OR): 1.123, 95% confidence interval (CI): 1.066-1.184, P < 0.001). Serum ANGPTL8 and ANGPTL8 + TyG index predicted MAFLD [area under the curve (AUC): 0.832 and 0.886, respectively; both P < 0.05]. Compared with MAFLD patients without fibrosis, those with fibrosis had higher serum ANGPTL8 and TyG index (both P < 0.05), and both parameters were positively correlated with MAFLD-associated fibrosis. Elevated serum ANGPTL8 (OR: 1.093, 95%CI: 1.044-1.144, P < 0.001) and TyG index (OR: 2.383, 95%CI: 1.199-4.736, P < 0.013) were risk factors for MAFLD-associated fibrosis. Serum ANGPTL8 and ANGPTL8 + TyG index predicted MAFLD-associated fibrosis (AUC: 0.812 and 0.835, respectively; both P < 0.05). CONCLUSION: The serum levels of ANGPTL8 are elevated and positively correlated with MAFLD. They can serve as predictors for the risk of MAFLD and liver fibrosis, with the ANGPTL8 + TyG index potentially exhibiting even higher predictive value.

13.
World J Gastrointest Surg ; 16(2): 419-428, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38463360

RESUMO

BACKGROUND: The common clinical method to evaluate blood loss during pancreaticoduodenectomy (PD) is visual inspection, but most scholars believe that this method is extremely subjective and inaccurate. Currently, there is no accurate, objective method to evaluate the amount of blood loss in PD patients. AIM: The hemoglobin (Hb) loss method was used to analyze the amount of blood loss during PD, which was compared with the blood loss estimated by traditional visual methods. The risk factors for bleeding were also predicted at the same time. METHODS: We retrospectively analyzed the clinical data of 341 patients who underwent PD in Shandong Provincial Hospital from March 2017 to February 2019. According to different surgical methods, they were divided into an open PD (OPD) group and a laparoscopic PD (LPD) group. The differences and correlations between the intraoperative estimation of blood loss (IEBL) obtained by visual inspection and the intraoperative calculation of blood loss (ICBL) obtained using the Hb loss method were analyzed. ICBL, IEBL and perioperative calculation of blood loss (PCBL) were compared between the two groups, and single-factor regression analysis was performed. RESULTS: There was no statistically significant difference in the preoperative general patient information between the two groups (P > 0.05). PD had an ICBL of 743.2 (393.0, 1173.1) mL and an IEBL of 100.0 (50.0, 300.0) mL (P < 0.001). There was also a certain correlation between the two (r = 0.312, P < 0.001). Single-factor analysis of ICBL showed that a history of diabetes [95% confidence interval (CI): 53.82-549.62; P = 0.017] was an independent risk factor for ICBL. In addition, the single-factor analysis of PCBL showed that body mass index (BMI) (95%CI: 0.62-76.75; P = 0.046) and preoperative total bilirubin > 200 µmol/L (95%CI: 7.09-644.26; P = 0.045) were independent risk factors for PCBL. The ICBLs of the LPD group and OPD group were 767.7 (435.4, 1249.0) mL and 663.8 (347.7, 1138.2) mL, respectively (P > 0.05). The IEBL of the LPD group 200.0 (50.0, 200.0) mL was slightly greater than that of the OPD group 100.0 (50.0, 300.0) mL (P > 0.05). PCBL was greater in the LPD group than the OPD group [1061.6 (612.3, 1632.3) mL vs 806.1 (375.9, 1347.6) mL] (P < 0.05). CONCLUSION: The ICBL in patients who underwent PD was greater than the IEBL, but there is a certain correlation between the two. The Hb loss method can be used to evaluate intraoperative blood loss. A history of diabetes, preoperative bilirubin > 200 µmol/L and high BMI increase the patient's risk of bleeding.

14.
Biomacromolecules ; 25(4): 2423-2437, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457661

RESUMO

Chronic infected wounds often fail to heal through normal repair mechanisms, and the persistent response of reactive oxygen species (ROS) and inflammation is a major contributing factor to the difficulty in their healing. In this context, we developed an ROS-responsive injectable hydrogel. This hydrogel is composed of ε-polylysine grafted (EPL) with caffeic acid (CA) and hyaluronic acid (HA) grafted with phenylboronic acid (PBA). Before the gelation process, a mixture CaO2@Cur-PDA (CCP) consisting of calcium peroxide (CaO2) coated with polydopamine (PDA) and curcumin (Cur) is embedded into the hydrogel. Under the conditions of chronic refractory wound environments, the hydrogel gradually dissociates. HA mimics the function of the extracellular matrix, while the released caffeic acid-grafted ε-polylysine (CE) effectively eliminates bacteria in the wound vicinity. Additionally, released CA also clears ROS and influences macrophage polarization. Subsequently, CCP further decomposes, releasing Cur, which promotes angiogenesis. This multifunctional hydrogel accelerates the repair of diabetic skin wounds infected with Staphylococcus aureus in vivo and holds promise as a candidate dressing for the healing of chronic refractory wounds.


Assuntos
Anti-Infecciosos , Ácidos Cafeicos , Curcumina , Hidrogéis/farmacologia , Polilisina/farmacologia , Espécies Reativas de Oxigênio , Curcumina/farmacologia , Ácido Hialurônico/farmacologia , Antibacterianos/farmacologia
15.
BMC Nurs ; 23(1): 194, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38520023

RESUMO

OBJECTIVE: This study aims to investigate the relationship between psychological resilience, thriving at work, and work performance among nurses, as well as analyse the mediating role of thriving at work in the relationship between psychological resilience and the work performance of nurses. The findings are intended to serve as a reference for nursing managers to design tailored work performance intervention programs. METHOD: Using convenience sampling, 308 clinical nurses were selected from a tertiary hospital in Changsha City, Hunan Province, China, from February to April 2023. The Connor-Davidson Resilience Scale (CD-RISC), the Thriving at Work Scale, and the Work Performance Scale were employed for the questionnaire survey. Pearson correlation analysis was used to explore the relationship between psychological resilience, thriving at work and work performance. The SPSS 26.0 software's 'Process' plugin was utilised for mediation effect analysis. RESULTS: Significantly positive correlations were found between psychological resilience and thriving at work (r = 0.806, P < 0.01), thriving at work and work performance (r = 0.571, P < 0.01) as well as psychological resilience and work performance (r = 0.572, P < 0.01). Psychological resilience significantly predicted work performance positively (ß = 0.558, t = 11.165, P < 0.01), and this prediction remained significant when thriving at work (the mediating variable), was introduced (ß = 0.371, t = 4.772, P < 0.01). Psychological resilience significantly predicted thriving at work positively (ß = 0.731, t = 20.779, P < 0.01), and thriving at work significantly predicted work performance positively (ß = 0.256, t = 3.105, P < 0.05). The mediating effect size of thriving at work between psychological resilience and work performance was 33.49% (P < 0.05). CONCLUSION: Thriving at work plays a partial mediating role between psychological resilience and work performance. The level of work performance among clinical nurses was relatively high. Nursing managers can enhance thriving at work by fostering psychological resilience among clinical nurses, thereby further improving their work performance to ensure high-quality and efficient nursing care.

16.
J Agric Food Chem ; 72(12): 6711-6722, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38491973

RESUMO

Through bioassay-guided isolation, eight undescribed coumarins (1-8), along with six reported coumarins (9-14), were obtained from Coriaria nepalensis. The new structures were determined by using IR, UV, NMR, HRESIMS, and ECD calculations. The results of the biological activity assays showed that compound 9 exhibited broad spectrum antifungal activities against all tested fungi in vitro and a significant inhibitory effect on Phytophthora nicotianae with an EC50 value of 3.00 µg/mL. Notably, compound 9 demonstrated greater curative and protective effects against tobacco balack shank than those of osthol in vivo. Thus, 9 was structurally modified to obtain new promising antifungal agents, and the novel derivatives (17b, 17j, and 17k) exhibited better effects on Sclerotinia sclerotiorum than did lead compound 9. Preliminary mechanistic exploration illustrated that 9 could enhance cell membrane permeability, destroy the morphology and ultrastructure of cells, and reduce the exopolysaccharide content of P. nicotianae mycelia. Furthermore, the cytotoxicity results revealed that compound 9 exhibited relatively low cytotoxicity against HEK293 cell lines with an inhibition rate of 33.54% at 30 µg/mL. This research is promising for the discovery of new fungicides from natural coumarins with satisfactory ecological compatibility.


Assuntos
Fungicidas Industriais , Magnoliopsida , Humanos , Células HEK293 , Fungicidas Industriais/química , Antifúngicos/farmacologia , Tabaco , Cumarínicos/química , Relação Estrutura-Atividade
18.
J Basic Microbiol ; : e202300441, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38470163

RESUMO

High-temperature-requirement protein A (HtrA) family proteins play important roles in controlling protein quality and are recognized as virulence factors in numerous animal and human bacterial pathogens. The role of HtrA family proteins in plant pathogens remains largely unexplored. Here, we investigated the HtrA family protein, DegQ, in the crucifer black rot pathogen Xanthomonas campestris pathovar campestris (Xcc). DegQ is essential for bacterial attachment and full virulence of Xcc. Moreover, the degQ mutant strain showed increased sensitivity to heat treatment and sodium dodecyl sulfate. Expressing the intact degQ gene in trans in the degQ mutant could reverse the observed phenotypic changes. In addition, we demonstrated that the DegQ protein exhibited chaperone-like activity. Transcriptional analysis displayed that degQ expression was induced under heat treatment. Our results contribute to understanding the function and expression of DegQ of Xcc for the first time and provide a novel perspective about HtrA family proteins in plant pathogen.

19.
Zhongguo Gu Shang ; 37(2): 114-119, 2024 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-38425059

RESUMO

OBJECTIVE: To explore and compare the clinical efficacy of orthopedic robot assisted femoral neck system (FNS) and traditional manual FNS in the treatment of femoral neck fractures in middle-aged and young people. METHODS: The clinical data of 62 consecutive patients with femoral neck fracture and age less than 65 years old admitted to the Intelligent Orthopaedic Department of Beijing Jishuitan Hospital from June 2021 to June 2022 were retrospectively analyzed. According to whether orthopedic robot-assisted surgery the patients were divided into two groups:30 patients aged 34 to 56 years old were treated with orthopedic robot assisted FNS internal fixation after closed or limited open reduction(experimental group); 32 patients aged 33 to 54 years old underwent FNS internal fixation after closed or limited open reduction(control group). The age, gender, time from injury to admission, average hospital stay, surgical duration, intraoperative bleeding volume, and intraoperative fluoroscopy frequency of two groups of patients were analyzed and compared. The hip joint function in both groups of patients was evaluated using the Harris hip joint scoring standard at 6 months after surgery. RESULTS: All 62 patients with femoral neck fractures successfully completed the surgery. There was no significant difference(P>0.05) between the experimental group and the control group in terms of baseline data such as age, gender, time from injury to admission, time from admission to surgery and the intraoperative bleeding. The surgical duration of the experimental group was significantly shorter than that of the control group [42.1(28.5, 50.7)min vs. 53.4(36.9, 62.5) min, Z=-2.338, P=0.019]. The intraoperative X-ray fluoroscopy frequency of the experimental group was significantly lower than that of the control group[8.0 (6.0, 11.0) times vs. 15.0(13.0, 17.0) times, Z=-5.960, P<0.001]. In terms of postoperative hip joint function, there was no significant difference in Harris score between the two groups of patients at 6-month follow-up(P>0.05). CONCLUSION: Compared with manual operation of FNS, orthopedic robot assisted FNS in the treatment of femoral neck fractures can help shorten surgical time, reduce intraoperative fluoroscopy frequency, and have similar therapeutic effects on long-term hip joint function recovery.


Assuntos
Fraturas do Colo Femoral , Ortopedia , Robótica , Pessoa de Meia-Idade , Humanos , Adolescente , Idoso , Adulto , Colo do Fêmur , Estudos Retrospectivos , Fraturas do Colo Femoral/cirurgia , Resultado do Tratamento , Fixação Interna de Fraturas
20.
Zhongguo Gu Shang ; 37(2): 173-8, 2024 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-38425069

RESUMO

OBJECTIVE: To explore the efficacy of high tibial osteotomy (HTO) combined with medial meniscus centralization in knee osteoarthritis. METHODS: A total of 26 patients who underwent surgery from October 2018 to October 2020 were reviewed. Among them, 14 patients underwent high tibial osteotomy combined with arthroscopic meniscus centralization surgery were centralized group, including 8 males and 6 females, with an average age of (50.2±1.4) years old and follow-up time of (16.8±4.0) months. Twelve patients with high tibial osteotomy were in the control group, including 6 males and 6 females, with an average age of (50.9±1.8) years and follow-up time of (19.0±4.8) months. Operation time, the knee Lysholm score, knee 2000 IKDC score, MRI, femoral tibial angle(FTA), hip knee ankle angle (HKA), and intraoperative and postoperative complications were recorded. RESULTS: All the incisions healed without any complication. The operation time in the centralized group was longer than that in the control group[(65.0±2.1)min vs(52.0±2.1)min, P<0.05]. The medial meniscus extrusion reduction value in the centralized group was significantly reduced compared with the control group[(2.8±1.4) mm vs (1.1±2.2) mm, P<0.05]. The FTA, HKA, knee Lyshlom score, and 2000 IKDC score between two groups were no significantly (P>0.05). Postoperative knee Lyshlom score and knee 2000 IKDC score improved in both groups(P<0.05). CONCLUSION: HTO combined with centralization of medial meniscus can improve the reduction of medial meniscus and improve knee function. The medium and long-term curative effect still needs long-term follow-up of more cases.


Assuntos
Osteoartrite do Joelho , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Osteoartrite do Joelho/cirurgia , Meniscos Tibiais/cirurgia , Resultado do Tratamento , Articulação do Joelho/cirurgia , Tíbia/cirurgia , Osteotomia , Estudos Retrospectivos
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