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1.
Angew Chem Int Ed Engl ; : e202412020, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38993096

RESUMO

Mutualisms are interactions that benefit all species involved. It has been widely investigated in neighbouring subjects, such as biology, ecology, sociology, and economics. However, such a reciprocal relationship in synthetic chemical systems has rarely been studied. Here, we demonstrate a mutualistic synthesis where byproducts from two orthogonal chemical reactions aid each other's production. Disulfide exchange and hydrazone exchange were chosen to generate two dynamic combinatorial libraries. A minor tetrameric macrocycle from the active disulfide library was quantitatively amplified in the presence of the hydrazone library. This incorporation also turned on the previously inert hydrazone reaction, producing a linear species that formed a "handcuffs" catenane with the disulfide tetramer. These findings not only lend robust support to the hypothesis of "RNA-peptide coevolution" for the origin of life but also broaden the scope of synthetic chemistry, highlighting the untapped potential of minor products from different reactions. Additionally, the co-self-assembly of these mutualistic entities to form supramolecular structures opens new avenues for future development of composite nanosystems with synergistic properties.

2.
Clin Res Hepatol Gastroenterol ; 48(7): 102413, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38960124

RESUMO

BACKGROUND: Prior typing methods fail to provide predictive insights into surgical complexities for extrahepatic choledochal cyst (ECC). This study aims to establish a new classification system for ECC through clustering of imaging results. Additionally, it seeks to compare the differences among the identified ECC types and assess the levels of surgical difficulty. METHODS: The imaging data of 124 patients were automatically grouped through a K-means clustering analysis. According to the characteristics of the new grouping, corrections and interventions were carried out to establish a new classification. Demographic data, clinical presentations, surgical parameters, complications, reoperation, and prognostic indicators were analyzed according to different types. Factors contributing to prolonged surgical time were also evaluated. RESULTS: A new classification system of ECC: Type A (upper segment), Type B (middle segment), Type C (lower segment), and Type D (entire bile duct). The incidences of comorbidities (calculus or infection) were significantly different (P = 0.000, P = 0.002). Additionally, variations in the incidence of postoperative biliary stricture were statistically significant (P = 0.046). The operative time was significantly different between groups (P = 0.001). Age, BMI > 30, classification, and the presence of combined stones exhibit a significant association with prolonged operative time (P = 0.002, P = 0.000, P = 0.011, P = 0.011). CONCLUSION: In conclusion, our utilization of machine learning-driven cluster analysis has enabled the creation of a novel extrahepatic biliary dilatation typology. This classification, in conjunction with factors like age, combined stone occurrence, and obesity, significantly influences the complexity of laparoscopic choledochal cyst surgery, offering valuable insights for improved surgical treatment.

3.
Sensors (Basel) ; 24(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-39000934

RESUMO

SAR (synthetic aperture radar) ship detection is a hot topic due to the breadth of its application. However, limited by the volume of the SAR image, the generalization ability of the detector is low, which makes it difficult to adapt to new scenes. Although many data augmentation methods-for example, clipping, pasting, and mixing-are used, the accuracy is improved little. In order to solve this problem, the adversarial training is used for data generation in this paper. Perturbation is added to the SAR image to generate new samples for training, and it can make the detector learn more abundant features and promote the robustness of the detector. By separating batch normalization between clean samples and disturbed images, the performance degradation on clean samples is avoided. By simultaneously perturbing and selecting large losses of classification and location, it can keep the detector adaptable to more confrontational samples. The optimization efficiency and results are improved through K-step average perturbation and one-step gradient descent. The experiments on different detectors show that the proposed method achieves 8%, 10%, and 17% AP (Average Precision) improvement on the SSDD, SAR-Ship-Dataset, and AIR-SARShip, compared to the traditional data augmentation methods.

4.
Hepatology ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985995

RESUMO

BACKGROUND AND AIMS: Inflammatory response is crucial for bile acid (BA)-induced cholestatic liver injury, but molecular mechanisms remain to be elucidated. Solute Carrier Family 35 Member C1 (SLC35C1) can transport GDP-fucose into the Golgi to facilitate protein glycosylation. Its mutation leads to the deficiency of leukocyte adhesion and enhances inflammation in humans. However, little is known about its role in liver diseases. APPROACH AND RESULTS: Hepatic SLC35C1 mRNA transcripts and protein expression were significantly increased in patients with obstructive cholestasis (OC) and mouse models of cholestasis. Immunofluorescence revealed that the upregulated SLC35C1 expression mainly occurred in hepatocytes. Liver-specific ablation of Slc35c1 (Slc35c1 cKO) significantly aggravated liver injury in mouse models of cholestasis induced by bile duct ligation and 1% cholic acid-feeding, evidenced by increased liver necrosis, inflammation, fibrosis, and bile ductular proliferation. The Slc35c1 cKO increased hepatic chemokine Ccl2 and Cxcl2 expression and T-cell, neutrophil and F4/80 macrophage infiltration, but did not affect the levels of serum and liver BA in mouse models of cholestasis. LC-MS/MS analysis revealed that hepatic Slc35c1 deficiency substantially reduced the fucosylation of cell-cell adhesion protein CEACAM1 at N153. Mechanistically, cholestatic levels of conjugated BAs stimulated SLC35C1 expression by activating the STAT3 signaling to facilitate CEACAM1 fucosylation at N153, and deficiency in the fucosylation of CEACAM1 at N135 enhanced the BA-stimulated CCL2 and CXCL2 mRNA expression in primary mouse hepatocytes and PLC/PRF/5-ASBT cells. CONCLUSIONS: Elevated hepatic SLC35C1 expression attenuates cholestatic liver injury by enhancing CEACAM1 fucosylation to suppress CCL2 and CXCL2 expression and liver inflammation.

5.
Ann Surg Oncol ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38995449

RESUMO

BACKGROUND: Because of the complex anatomy of the right posterior hepatic pedicle, there have been few reports on standardized laparoscopic portal territory staining-guided anatomical resection of liver segment 6 (LPTAR-S6). This study aimed to elucidate the indocyanine green (ICG) fluorescence staining methods for LPTAR-S6. PATIENTS AND METHODS: LPTAR-S6 can be performed using positive and negative fluorescence staining approaches. We implemented these two approaches for patients with hepatocellular carcinoma. Descriptions of the surgical strategy and technical details are presented. RESULTS: Two patients safely underwent LPTAR-S6 using a preoperative three-dimensional reconstruction plan. The intraoperative ICG fluorescence staining effect was satisfactory, and the anatomical landmarks were fully exposed. CONCLUSIONS: A detailed preoperative three-dimensional reconstruction plan, complete intraoperative application of real-time laparoscopic ultrasound guidance, and ICG fluorescence staining can result in accurate transection of the liver parenchyma during LPTAR-S6.

6.
Int J Med Sci ; 21(9): 1718-1729, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006833

RESUMO

Isoproterenol (ISO) administration is a well-established model for inducing myocardial injury, replicating key features of human myocardial infarction (MI). The ensuing inflammatory response plays a pivotal role in the progression of adverse cardiac remodeling, characterized by myocardial dysfunction, fibrosis, and hypertrophy. The Mst1/Hippo signaling pathway, a critical regulator of cellular processes, has emerged as a potential therapeutic target in cardiovascular diseases. This study investigates the role of Mst1 in ISO-induced myocardial injury and explores its underlying mechanisms. Our findings demonstrate that Mst1 ablation in cardiomyocytes attenuates ISO-induced cardiac dysfunction, preserving cardiomyocyte viability and function. Mechanistically, Mst1 deletion inhibits cardiomyocyte apoptosis, oxidative stress, and calcium overload, key contributors to myocardial injury. Furthermore, Mst1 ablation mitigates endoplasmic reticulum (ER) stress and mitochondrial fission, both of which are implicated in ISO-mediated cardiac damage. Additionally, Mst1 plays a crucial role in modulating the inflammatory response following ISO treatment, as its deletion suppresses pro-inflammatory cytokine expression and neutrophil infiltration. To further investigate the molecular mechanisms underlying ISO-induced myocardial injury, we conducted a bioinformatics analysis using the GSE207581 dataset. GO and KEGG pathway enrichment analyses revealed significant enrichment of genes associated with DNA damage response, DNA repair, protein ubiquitination, chromatin organization, autophagy, cell cycle, mTOR signaling, FoxO signaling, ubiquitin-mediated proteolysis, and nucleocytoplasmic transport. These findings underscore the significance of Mst1 in ISO-induced myocardial injury and highlight its potential as a therapeutic target for mitigating adverse cardiac remodeling. Further investigation into the intricate mechanisms of Mst1 signaling may pave the way for novel therapeutic interventions for myocardial infarction and heart failure.


Assuntos
Via de Sinalização Hippo , Isoproterenol , Infarto do Miocárdio , Miócitos Cardíacos , Proteínas Serina-Treonina Quinases , Transdução de Sinais , Animais , Isoproterenol/efeitos adversos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Miócitos Cardíacos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Camundongos , Humanos , Infarto do Miocárdio/patologia , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/genética , Remodelação Ventricular/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Apoptose/genética , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/genética , Inflamação/patologia , Modelos Animais de Doenças , Proteínas Proto-Oncogênicas , Fator de Crescimento de Hepatócito
7.
Transl Lung Cancer Res ; 13(6): 1232-1246, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38973946

RESUMO

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare, highly malignant type of non-small cell lung cancer (NSCLC) with a poor prognosis. Targeted drugs for MET exon 14 (METex14) skipping mutation can have considerable clinical benefits. This study aimed to predict METex14 skipping mutation in PSC patients by whole-tumour texture analysis combined with clinical and conventional contrast-enhanced computed tomography (CECT) features. Methods: This retrospective study included 56 patients with PSC diagnosed by pathology. All patients underwent CECT before surgery or other treatment, and both targeted DNA- and RNA-based next-generation sequencing (NGS) were used to detect METex14 skipping mutation status. The patients were divided into two groups: METex14 skipping mutation and nonmutation groups. Overall, 1,316 texture features of the whole tumour were extracted. We also collected 12 clinical and 20 conventional CECT features. After dimensionality reduction and selection, predictive models were established by multivariate logistic regression analysis. Models were evaluated using the area under the curve (AUC), and the clinical utility of the model was assessed by decision curve analysis. Results: METex14 skipping mutation was detected in 17.9% of PSCs. Mutations were found more frequently in those (I) who had smaller long- or short-axis diameters (P=0.02, P=0.01); (II) who had lower T stages (I, II) (P=0.02); and (III) with pseudocapsular or annular enhancement (P=0.03). The combined model based on the conventional and texture models yielded the best performance in predicting METex14 skipping mutation with the highest AUC (0.89). The conventional and texture models also had good performance (AUC =0.83 conventional; =0.88 texture). Conclusions: Whole-tumour texture analysis combined with clinical and conventional CECT features may serve as a noninvasive tool to predict the METex14 skipping mutation status in PSC.

8.
Eur Radiol ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980413

RESUMO

OBJECTIVES: To compare the safety and efficiency of ultrasound-guided percutaneous radiofrequency ablation (RFA) and surgical resection (SR) for thyroid papillary carcinoma (PTC) in the danger triangle area. METHODS: The clinical data of 298 patients who underwent either percutaneous RFA or SR for PTC in the thyroid danger triangle at our hospital between January 2018 and April 2020 were retrospectively analyzed. Propensity score matching is employed to regulate for confounding factors. All patients undergoing ablation were treated using a strategy that combined sufficient paratracheal fluid isolation with a low-power, short electrode. Disease progression was analyzed in patients with T1N0M0 PTC (T1a and T1b) employed in Kaplan‒Meier curves. Treatment parameters and the rates of local recurrence, distant metastasis, and complications are recorded and compared. RESULTS: Of 182 eligible patients who were included, 91 were in the RFA (age 44.84 ± 13.19; 71 females; 77 T1a) and 91 were in the SR (age 47.36 ± 11.05; 68 females; 69 T1a). The average treatment time, length of hospital stays, blood loss volume, and scar length are substantially less in the RFA than in the SR. Major complications as well as postoperative permanent recurrent laryngeal nerve injury and postoperative transient parathyroid dysfunction occurred only in the SR, with a substantial distinction between the two groups (p < 0.05). There is no substantial distinction in the disease progression between RFA and SR treatment of T1N0M0 PTC. CONCLUSION: RFA is as effective as surgery for PTC in the danger triangle area in the short term, with faster recovery and fewer complications. CLINICAL RELEVANCE STATEMENT: Radiofrequency ablation has a clinical efficacy comparable to surgery in the treatment of papillary thyroid carcinoma in the danger triangle area in the short term with the advantages of faster recovery and fewer complications when compared with surgery. KEY POINTS: Use of radiofrequency ablation (RFA) in the thyroid danger triangle is still controversial. RFA and surgery groups showed no difference in disease progressions, and no major complications occurred with RFA. Radiofrequency ablation offers a new option for papillary thyroid carcinoma patients in the danger triangle.

9.
Wideochir Inne Tech Maloinwazyjne ; 19(1): 113-121, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38974758

RESUMO

Introduction: The incidence of renal tumours is increasing annually, and imaging alone cannot meet the diagnostic needs. Aim: This single-centre study aimed to evaluate the predictors of diagnostic imaging-guided percutaneous renal mass biopsy (PRMB), its accuracy and safety, and subsequent changes to the treatment plan. Material and methods: We retrospectively collected the clinical data of patients who had undergone PRMB. The diagnosis rate, pathological data, and complications were analysed. Potential predictors of a diagnostic PRMB were evaluated using logistic regression analysis. Changes to the treatment plan due to PRMB results were also analysed. Results: A total of 158 patients were included in this study. The univariate analysis showed that higher tumour diameter (OR = 1.223, 95% CI: 1.018-1.468, p = 0.031) and number of biopsy cores ≥ 2 (OR = 6.125, 95% CI: 2.006-18.703, p = 0.001) were significantly associated with diagnostic biopsy, and multivariate analysis results showed that higher tumour diameter (OR = 1.215, 95% CI: 1.008-1.463, p = 0.041) was an independent predictor of diagnostic biopsy. A nomogram including tumour diameter and number of biopsy cores was constructed to predict diagnostic biopsy. Compared with postoperative pathology, the concordance between biopsy and postoperative pathology at identifying malignancies, histologic type, and histologic grade were 100% (47/47), 85.1% (40/47), and 54.1% (20/37), respectively. The treatment plans of 15 patients (9.5%) changed based on the PRMB results. Fourteen patients (8.9%) had minor complications (Clavien-Dindo classification < 2). Conclusions: Our results suggest that tumour diameter was an independent predictor of diagnostic biopsy. Furthermore, PRMB can be accurately and safely performed and may guide clinical decision-making for patients with renal tumours.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38980998

RESUMO

Conductive hydrogels (CHs) are emerging materials for next generation sensing systems in flexible electronics. However, the fabrication of competent CHs with excellent stretchability, adhesion, self-healing, photothermal conversion, multisensing, and environmental stability remains a huge challenge. Herein, a nanocomposite organohydrogel with the above features is constructed by in situ copolymerization of zwitterionic monomer and acrylamide in the existence of carboxylic cellulose nanofiber-carrying reduced graphene oxide (rGO) plus a solvent displacement strategy. The synergy of abundant dipole-dipole interactions and intermolecular hydrogen bonds enables the organohydrogel to exhibit high stretchability, strong adhesion, and good self-healing. The presence of glycerol weakens the formation of hydrogen bonds between water molecules, endowing the organohydrogel with excellent environmental stability (-40 to 60 °C) to adapt to different application scenarios. Importantly, the multimodal organohydrogel presents excellent sensing behavior, including a high gauge factor of 16.3 at strains of 400-1440% and a reliable thermal coefficient of resistance (-4.2 °C-1) over a wide temperature widow (-40 to 60 °C). Moreover, the organohydrogel displays a highly efficient and reliable photothermal conversion ability due to the favorable optical absorbing behavior of rGO. Notably, the organohydrogel can detect accurate human activities at ambient temperature, demonstrating potential applications in flexible intelligent electronics.

11.
Biomaterials ; 311: 122687, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38941683

RESUMO

Obesity is a major public burden on the working population and induces chronic diseases. Its treatment often requires long-term medication, which makes patient compliance difficult. In this study, we reported the value of HORN-MN, which comprised a fast-soluble hyaluronic acid microneedle matrix and a weak acid-degradable oleanolic acid dimer of rosiglitazone nanoparticles. The results showed that the microneedles easily punctured the stratum corneum and dissolved in the dermis of the abdominal wall within 5 min, followed by the release of rosiglitazone nanoparticles. Thereafter, the nanoparticles were endocytosed by macrophages and white adipocytes, then degraded to oleanolic acid in the lysosomes, thereby, releasing rosiglitazone. Oleanolic acid significantly improved the inflammatory status of obese adipose tissue and promoted white adipocyte browning, and rosiglitazone significantly potentiated WAC browning. Accordingly, the patch demonstrated a remarkable obesity-reducing efficacy in mice. In conclusion, this study developed a quick paster type of soluble rosiglitazone nanoparticle microneedle for the treatment of obesity. This patch can be suitable for working people, with an evident obesity-reducing efficacy but no effect on skin integrity despite multiple administrations.

12.
Adv Sci (Weinh) ; : e2404513, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937993

RESUMO

Zinc anodes of zinc metal batteries suffer from unsatisfactory plating/striping reversibility due to interfacial parasitic reactions and poor Zn2+ mass transfer kinetics. Herein, methoxy polyethylene glycol-phosphate (mPEG-P) is introduced as an electrolyte additive to achieve long anti-calendar aging and high-rate capabilities. The polyanionic of mPEG-P self-assembles via noncovalent-interactions on electrode surface to form polyether-based cation channels and in situ organic-inorganic hybrid solid electrolyte interface layer, which ensure rapid Zn2+ mass transfer and suppresses interfacial parasitic reactions, realizing outstanding cycling/calendar aging stability. As a result, the Zn//Zn symmetric cells with mPEG-P present long lifespans over 9000 and 2500 cycles at ultrahigh current densities of 120 and 200 mA cm-2, respectively. Besides, the coulombic efficiency (CE) of the Zn//Cu cell with mPEG-P additive (88.21%) is much higher than that of the cell (36.4%) at the initial cycle after the 15-day calendar aging treatment, presenting excellent anti-static corrosion performance. Furthermore, after 20-day aging, the Zn//MnO2 cell exhibits a superior capacity retention of 89% compared with that of the cell without mPEG-P (28%) after 150 cycles. This study provides a promising avenue for boosting the development of high efficiency and durable metallic zinc based stationary energy storage system.

13.
Insects ; 15(6)2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38921170

RESUMO

Ecosystem engineers influence the structure and function of soil food webs through non-trophic interactions. The activity of large soil animals, such as earthworms, has a significant impact on the soil microarthropod community. However, the influence of millipedes on soil microarthropod communities remains largely unknown. In this microcosm experiment, we examined the effects of adding, removing, and restricting millipede activity on Acari and Collembola communities in litter and soil by conducting two destructive sampling sessions on days 10 and 30, respectively. At the time of the first sampling event (10 d), Acari and Collembola abundance was shown to increase and the alpha diversity went higher in the treatments with millipedes. At the time of the second sampling event (30 d), millipedes significantly reduced the Collembola abundance and alpha diversity. The results were even more pronounced as the millipedes moved through the soil, which caused the collembolans to be more inclined to inhabit the litter, which in turn resulted in the increase in the abundance and diversity of Acari in the soil. The rapid growth of Collembola in the absence of millipedes significantly inhibited the abundance of Acari. The presence of millipedes altered the community structure of Acari and Collembola, leading to a stronger correlation between the two communities. Changes in these communities were driven by the dominant taxa of Acari and Collembola. These findings suggest that millipedes, as key ecosystem engineers, have varying impacts on different soil microarthropods. This study enhances our understanding of biological interactions and offers a theoretical foundation for soil biodiversity conservation.

14.
Sci Total Environ ; 946: 174048, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38906282

RESUMO

RATIONALE: The association between ambient coarse particulate matter (PM2.5-10) and mortality in multi-drug resistant tuberculosis (MDR-TB) patients has not yet been studied. The modifying effects of temperature and humidity on this association are completely unknown. OBJECTIVES: To evaluate the effects of long-term PM2.5-10 exposures, and their modifications by temperature and humidity on mortality among MDR-TB patients. METHODS: A Chinese cohort of 3469 MDR-TB patients was followed up from diagnosis until death, loss to follow-up, or the study's end, averaging 2567 days per patient. PM2.5-10 concentrations were derived from the difference between PM10 and PM2.5. Cox proportional hazard models estimated hazard ratios (HRs) per 3.74 µg/m3 (interquartile range, IQR) exposure to PM2.5-10 and all-cause mortality for the full cohort and individuals at distinct long-term and short-term temperature and humidity levels, adjusting for other air pollutants and potential covariates. Exposure-response relationships were quantified using smoothed splines. RESULTS: Hazard ratios of 1.733 (95% CI, 1.407, 2.135) and 1.427 (1.114, 1.827) were observed for mortality in association with PM2.5-10 exposures for the full cohort under both long-term and short-term exposures to temperature and humidity. Modifying effects by temperature and humidity were heterogenous across sexes, age, treatment history, and surrounding environment measured by greenness and nighttime light levels. Nonlinear exposure-response curves suggestes a cumulative risk of PM2.5-10-related mortality starting from a low exposure concentration around 15 µg/m3. CONCLUSION: Long-term exposure to PM2.5-10 poses significant harm among MDR-TB patients, with effects modified by temperature and humidity. Immediate surveillance of PM2.5-10 is crucial to mitigate the progression of MDR-TB severity, particularly due to co-exposures to air pollution and adverse weather conditions.

15.
Hepatobiliary Surg Nutr ; 13(3): 494-499, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38911193

RESUMO

Laparoscopic anatomical hepatectomy (LAH) for patients with hepatocellular carcinoma (HCC) has been advocated by many surgeons in the hope of producing better oncological outcomes. Two recent techniques, 3D laparoscopic system and 2D real-time indocyanine green fluorescence imaging (r-ICG) guidance, are benefit for improving the operative precision of LAH in different aspects. However, these two techniques cannot be applied concomitantly because of the technical limitation. Although a new modern laparoscopic system with both 3D and indocyanine green (ICG) imaging mode has been designed, it has not been listed in many countries including China. Thus, we design a new procedure to perform the 3D LAH with 2D r-ICG guidance for HCCs with conventional laparoscopic systems. In this procedure, both 3D and 2D laparoscopic systems were used. A total of 11 patients with HCC received 3D laparoscopic right posterior sectionectomy (LRPS) with 2D r-ICG guidance. The right posterior Glissonian pedicle was clamped under the 3D vision. Then ICG solution was then intravenously administrated. The liver parenchyma was transected under the 3D vision and guided by 2D ICG vision simultaneously. There was no severe complications (Clavien-Dindo ≥III) and operation related death. The 90-day mortality was also nil. By using this procedure, the advantages of two techniques, 3D laparoscopic system and 2D r-ICG guidance, were combined so that LAH could be performed with more precision. However, it should be validated in more studies.

18.
Mol Biomed ; 5(1): 23, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38871861

RESUMO

Sleep deprivation (SD) has emerged as a critical concern impacting human health, leading to significant damage to the cardiovascular system. However, the underlying mechanisms are still unclear, and the development of targeted drugs is lagging. Here, we used mice to explore the effects of prolonged SD on cardiac structure and function. Echocardiography analysis revealed that cardiac function was significantly decreased in mice after five weeks of SD. Real-time quantitative PCR (RT-q-PCR) and Masson staining analysis showed that cardiac remodeling marker gene Anp (atrial natriuretic peptide) and fibrosis were increased, Elisa assay of serum showed that the levels of creatine kinase (CK), creatine kinase-MB (CK-MB), ANP, brain natriuretic peptide (BNP) and cardiac troponin T (cTn-T) were increased after SD, suggesting that cardiac remodeling and injury occurred. Transcript sequencing analysis indicated that genes involved in the regulation of calcium signaling pathway, dilated cardiomyopathy, and cardiac muscle contraction were changed after SD. Accordingly, Western blotting analysis demonstrated that the cardiac-contraction associated CaMKK2/AMPK/cTNI pathway was inhibited. Since our preliminary research has confirmed the vital role of Casein Kinase-2 -Interacting Protein-1 (CKIP-1, also known as PLEKHO1) in cardiac remodeling regulation. Here, we found the levels of the 3' untranslated region of Ckip-1 (Ckip-1 3'UTR) decreased, while the coding sequence of Ckip-1 (Ckip-1 CDS) remained unchanged after SD. Significantly, adenovirus-mediated overexpression of Ckip-1 3'UTR alleviated SD-induced cardiac dysfunction and remodeling by activating CaMKK2/AMPK/cTNI pathway, which proposed the therapeutic potential of Ckip-1 3'UTR in treating SD-induced heart disease.


Assuntos
Regiões 3' não Traduzidas , Proteínas Quinases Ativadas por AMP , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina , Transdução de Sinais , Privação do Sono , Animais , Masculino , Camundongos , Regiões 3' não Traduzidas/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/genética , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Miocárdio/patologia , Privação do Sono/genética , Privação do Sono/metabolismo , Privação do Sono/complicações , Troponina I/metabolismo , Troponina I/genética
19.
Bioresour Technol ; 406: 131018, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38908763

RESUMO

Higher nitrite accumulation, which is challenging to achieve reliably, is always sought to obtain better nitrogen removal performance in traditional partial nitritation-anammox (PN/A) process. This study developed a modified PN/A process by introducing nitrite-oxidizing bacteria and endogenous metabolism. Advanced nitrogen removal performance of 95.5 % was achieved at a low C/N ratio of 2.7 under nitrite accumulation ratio (NAR) fluctuations. Higher nitrate accumulation at lower NAR (70 âˆ¼ 40 %) resulted in superior anammox contribution (60 âˆ¼ 75 %) and nitrogen removal performance (93 âˆ¼ 98 %). This was attributed to the higher nitrogen removal efficiency of the post-anoxic endogenous partial denitrification coupling anammox process, although the PN/A process occurring first possessed a faster anammox rate of 2.0 mg NH4+-N /(g VSS⋅h). The introduction of nitrate allowed more nitrite flow to anammox, promoting a high enrichment of anammox bacteria (Ca. Brocadia, 0.3 % to 2.8 %). This study provides new insights into the practical application of the PN/A process.

20.
Angew Chem Int Ed Engl ; : e202408670, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38943429

RESUMO

Peptide folding is a dynamic process driven by non-covalent cross-linking leading to functional nanostructures for essential biochemical activities. However, replicating this process in synthetic systems is challenging due to the difficulty in mimicking nature's real-time regulation of non-covalent crosslinking for single-chain polymer folding. Here, we address this by employing anionic dithiol building blocks to create macrocyclic disulfides as non-covalent crosslinkers that adapted to the folding process. Initially, small macrocycles facilitated a low degree folding of a polycation. Then, this preorganized structure catalysed the production of larger macrocycles that enhanced the folding conversely. The self-adaptive synthesis was verified through the encapsulation of an anticancer drug, showing an updated production distribution of non-covalent crosslinkers and maximizing drug-loading efficiency against drug-resistant cancer in vitro. Our research advances the understanding of molecular systems by exploring species evolution via the structural dynamics of polymer folding. Additionally, adaptive synthesis enables controlled, sequential folding of synthetic polymers, with the potential to mimic protein functions.

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