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1.
J Phys Chem Lett ; : 8620-8627, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39146524

RESUMO

The radiative and photodissociative properties of the dicarbon molecule, C2, in high-lying electronic states are of utmost importance for modeling the photochemical processes that occur in various astronomical environments. Despite extensive spectroscopic studies in the last two centuries, the photodissociation properties of C2 are still largely unknown, particularly for quantum states in the vacuum ultraviolet (VUV) region. Here, the lifetimes of C2 for each individual rovibrational level in the recently identified 23Σg- state are measured for the first time using a VUV-pump-UV-probe photoionization scheme. The lifetimes are found to be strongly dependent on the rotational and vibrational quantum levels in the 23Σg- state. The strongly rotationally dependent lifetimes observed here indicate that the 23Σg- state may mainly undergo a predissociation process through couplings with nearby repulsive electronic states. The current observation could have important applications in modeling the interstellar medium and cometary comae.

2.
Semin Dial ; 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39120010

RESUMO

BACKGROUND: The purpose of this study is to investigate the prevalence and risk factor of cognitive frailty in patients undergoing maintenance hemodialysis. METHODS: Systematically searched PubMed, EmBase, Web of Science, Cochrane Library, SinoMed, China Knowledge Resource Integrated Database, Wanfang Database, and Weipu Database from inception until January 1, 2024. Two researchers were independently screened and cross-checked. Stata 15.1 software was used to perform the meta-analysis. RESULTS: A total of 15 articles were included, including 5398 patients. The results showed that the prevalence of cognitive frailty in patients undergoing maintenance hemodialysis was 24%. Among them, age (odds ratio [OR] = 1.33, 95% CI [1.16, 1.53]), waist circumference (OR = 1.05, 95% CI [1.03, 1.08]), malnutrition (OR = 2.91, 95% CI [1.94, 4.35]), comorbidities (OR = 1.93, 95% CI [1.47, 2.54]), stroke history (OR = 2.94, 95% CI [1.72, 5.03]), and depression (OR = 3.26, 95% CI [1.91, 5.57]) were the main risk factors for cognitive frailty in patients undergoing maintenance hemodialysis. Education level (OR = 0.48, 95% CI [0.31, 0.73]) was protective factors for cognitive frailty in patients undergoing maintenance hemodialysis. CONCLUSIONS: Current evidence showed that the prevalence of cognitive frailty in patients undergoing maintenance hemodialysis was high, and there were many risk factors. Therefore, early identification and intervention of cognitive frailty in maintenance hemodialysis patients should be carried out, which may be helpful to reduce the prevalence rate and occurrence of adverse events and improve the prognosis of patients.

3.
Mol Med Rep ; 30(4)2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39129301

RESUMO

Chitinase­3 like­protein­1 (CHI3L1), a glycoprotein belonging to the glycoside hydrolase family 18, binds to chitin; however, this protein lacks chitinase activity. Although CHI3L1 is not an enzyme capable of degrading chitin, it plays significant roles in abnormal glucose and lipid metabolism, indicating its involvement in metabolic disorders. In addition, CHI3L1 is considered a key player in inflammatory diseases, with clinical data suggesting its potential as a predictor of cardiovascular disease. CHI3L1 regulates the inflammatory response of various cell types, including macrophages, vascular smooth muscle cells and fibroblasts. In addition, CHI3L1 participates in vascular remodeling and fibrosis, contributing to the pathogenesis of cardiovascular disease. At present, research is focused on elucidating the role of CHI3L1 in cardiovascular disease. The present systematic review was conducted to comprehensively evaluate the effects of CHI3L1 on cardiovascular cells, and determine the potential implications in the occurrence and progression of cardiovascular disease. The present study may further the understanding of the involvement of CHI3L1 in cardiovascular pathology, demonstrating its potential as a therapeutic target or biomarker in the management of cardiovascular disease.


Assuntos
Biomarcadores , Doenças Cardiovasculares , Proteína 1 Semelhante à Quitinase-3 , Humanos , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Proteína 1 Semelhante à Quitinase-3/metabolismo , Animais , Fibroblastos/metabolismo
4.
Phytochemistry ; : 114245, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39134110

RESUMO

Kopsileuconines A-D (1-4), four monoterpenoid bisindole alkaloids with unprecedented skeletons, along with their biosynthetically related precursors (5-8) were isolated from the roots of Kopsia hainanensis. Compound 1 possessed an undescribed C-6-C-5' dimerization pattern of aspidofractinine-type alkaloids. Compounds 2-4 were rhazinilam-kopsine (2) and rhazinilam-aspidofractinine type (3 and 4) bisindole alkaloids with undescribed skeletons, respectively. Their structures with absolute configurations were fully accomplished by extensive spectroscopic analysis, quantum-chemical calculations, and X-ray crystallography. A plausible biosynthetic pathway for 1-4 was proposed. Compound 2 exhibited a significant inhibitory effect against human lung cancer cell lines PC9 (EGFR mutant), with an IC50 value of 15.07 ± 1.19 µM.

5.
J Phys Chem Lett ; : 8562-8568, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39140675

RESUMO

State-specific dynamics of the dipole-bound state (DBS) of the cryogenically cooled deprotonated 4,4'-biphenol anion have been investigated by picosecond time-resolved pump-probe spectroscopy. For DBS vibrational states below the electron-detachment threshold, the relaxation rate is slow to give a lifetime (τ) longer than ∼5 ns, and it is attributed to the nonvalence-to-valence orbital transformation. For the DBS resonances above the detachment threshold, however, the lifetime decreases with the activation of autodetachment, whereas the otherwise zeroth DBS modes seem to be randomized by intramolecular vibrational energy redistribution (IVR), as manifested in the biexponential transients. As the DBS internal energy increases further, the lifetime shows a monotonic decrease to give τ ∼ 50 ps at E'vib ∼ 1700 cm-1. This study demonstrates that IVR may play an important role in the autodetachment dynamics when the density of states rapidly increases with increasing vibrational energy, giving important implications for the electron-transfer dynamics taking place in large biological or astrochemical systems.

6.
Colloids Surf B Biointerfaces ; 243: 114140, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39111157

RESUMO

Excessive local accumulation of reactive oxygen species (ROS) in vulvovaginal candidiasis (VVC) leads to oxidative stress and aggravates inflammation. This study aimed to optimize and synthesize four ROS-sensitive polyethylene glycol (PEG)-boride polymers (PB, PCB, BPB, and BCPCB). A nanomicelle (BCPCB-K) was constructed using BCPCB-encapsulated ketoconazole (KTZ). Finally, the depolymerization principle and ROS-sensitive drug release of BCPCB-K as well as its anti-Candida albicans (CA) and therapeutic effects on mice with VVC were explored through in vitro and in vivo experiments. BCPCB-K exhibited low toxicity to mammalian cells in vitro and good biocompatibility in vivo. It also improved the dispersion and solubility of the hydrophobic drug KTZ. Furthermore, BCPCB-K simultaneously scavenged ROS and released the drug, thus facilitating the antifungal and VVC-treating effects of KTZ. Overall, the findings of this study broadened the application of ROS-sensitive materials in the drug-loading and antifungal fields and provided a strategy for VVC treatment.

7.
Ren Fail ; 46(2): 2367716, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39099468

RESUMO

OBJECTIVES: The aim of this study was to determine the strength of the association between frailty and adverse outcomes in patients undergoing maintenance hemodialysis. DESIGN: A systematic review and meta-analysis. SETTING AND PARTICIPANTS: Patients aged ≥18 years who were undergoing maintenance hemodialysis. METHODS: PubMed, Web of Science, Embase, the Cochrane Library, Scopus, the China Knowledge Resource Integrated Database, the Wanfang Database and the Weipu Database were searched from inception until 11 April 2024. The reviewers independently selected the studies, extracted the data and evaluated the quality of the studies. Stata 15.1 software was used to perform the meta-analysis. RESULTS: A total of 36 articles were included in this study, including 56,867 patients. The primary outcome events in this study were mortality, hospitalization, and vascular access events. The secondary outcomes were depression, cognitive impairment, falls, fracture, sleep disturbances, and quality of life. This study suggested that frailty was associated with mortality in patients undergoing maintenance hemodialysis [hazard ratio (HR), 1.97; 95% CI, 1.62-2.40]. Frailty increased the risk of mortality in patients [odds ratio (OR), 2.33; 95% CI, 1.47-3.68]. In addition, we found that frailty was significantly associated with hospitalization in patients undergoing maintenance hemodialysis (OR, 2.47; 95% CI, 1.52-4.03). Patients who were undergoing maintenance hemodialysis and who were frail had a greater risk of hospitalization [RR, 1.47; 95% CI, 1.05-2.08] and emergency visits (RR, 2.28; 95% CI, 1.78-2.92). The results of this study also suggested that frailty was associated with a greater risk of vascular access events (HR, 1.72; 95% CI, 1.50-1.97). Finally, frailty increased the risk of depression (OR, 4.31; 95% CI, 1.83-10.18), falls and fractures, and reduced quality of life. CONCLUSIONS: The findings of this study suggested that frailty was an important predictor of adverse outcomes in patients undergoing maintenance hemodialysis. In the future, medical staff should regularly evaluate signs of weakness, formulate individual diagnosis and treatment plans, adjust dialysis plans according to the patient's condition, and reduce the occurrence of adverse events. REGISTRATION: The study protocol was registered on PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, number: CRD42023486239).


Assuntos
Fragilidade , Hospitalização , Falência Renal Crônica , Qualidade de Vida , Diálise Renal , Humanos , Diálise Renal/efeitos adversos , Fragilidade/epidemiologia , Hospitalização/estatística & dados numéricos , Falência Renal Crônica/terapia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/complicações , Acidentes por Quedas/estatística & dados numéricos , Depressão/epidemiologia , Depressão/etiologia , Fatores de Risco
8.
Cardiology ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39089228

RESUMO

INTRODUCTION: Muscular ventricular septal defect occluders (MVSDO) have been attempted as an option in low-weight patients with patent ductus arteriosus (PDA). Few studies have assessed the safety of transcatheter patent ductus arteriosus closure (TCPC) using MVSDO. Therefore, we compared the outcomes in low-weight patients who used MVSDO and mushroom-shaped occluder (MSO). METHODS: Medical records of children under 10 kg (n=417) who underwent TCPC from 2015 to 2021 at a Chinese health center were reviewed. They were divided into MSO (n=372) and MVSDO (n=45) groups. A 1:1 propensity score matching (PSM) was done considering gender, height, weight, body surface area (BSA), PDA diameter, and BSA-corrected PDA diameter. RESULTS: All 45 children in the MVSDO group (mean weight: 5.92 ± 1.32 kg) achieved success immediate occlusion. One MVSDO migrated within 24 hours requiring unplanned surgery. MVSDO significantly ameliorated pulmonary artery hypertension. After PSM, each group comprised 41 children. The MVSDO group had a smaller effect on platelet counts (MVSDO vs. MSO =259.85 ± 114.82 vs. 356.12 ± 134.37, p < 0.001), a reduced incidence of thrombocytopenia (MVSDO vs. MSO = 2 vs. 7, p = 0.001), and a higher rate of residual shunting (MVSDO vs. MSO =16/41 vs. 5/41, p = 0.005), compared with the MSO group. Thrombocytopenia resolved during hospitalization and micro-shunts disappeared by six months. No pulmonary artery or descending aortic secondary stenosis was observed in one-year follow-up. CONCLUSIONS: MVSDO using in low-weight children is feasible, with high success and satisfactory postoperative and short-term follow-up outcomes, including lower thrombocytopenia incidence, compared to MSO. Further long-term studies with larger samples are recommended.

9.
World J Clin Cases ; 12(20): 4217-4229, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39015922

RESUMO

BACKGROUND: Pulmonary hypertension is a serious complication in the treatment of maintenance hemodialysis patients, which seriously affects the quality of life of patients and threatens their life safety. Prevention, treatment and improvement of pulmonary hypertension are of great significance to improve the quality of life of patients. AIM: To investigate the intervention and control of pedal-powered bicycle in maintaining quality of life and pulmonary hypertension in hemodialysis patients. METHODS: 73 patients with maintenance hemadialysis combined with pulmonary arterial hypertension at a hemodialysis center in a certain hospital from May 2021 to May 2022 are selected. Patients are divided into two groups, 37 cases in the control group (group C) and 36 cases in the intervention group (group I). Patients are divided into two groups, group C is treated with oral administration of betaglandin sodium combined with routine nursing care. Based on group C, group I conducts power cycling exercises. RESULTS: After treatment, group I patients had higher muscle strength, 36-Item Short Form Health Survey scores, and Kidney Disease Targets Areas scores; The 6-minute walk distance test index level was higher and the Borg score was lower; The group I had lower systolic blood pressure, greater vital capacity, higher positive emotion, lower systolic pulmonary artery pressure index level, higher arterial partial oxygen pressure level, lower pulmonary vascular resistance index level, and higher blood oxygen saturation level [158.91 ± 11.89 vs 152.56 ± 12.81, 1795.01 ± 603.18 vs 1907.20 ± 574.15, 24.00 (22.00, 29.00) vs 24.00 (22.00, 28.00), P < 0.001]. CONCLUSION: Aerobic exercise combined with Western medicine treatment can effectively improve patients' pulmonary hypertension, alleviate their negative emotions, and enable them to achieve a higher level of quality of life.

10.
Angew Chem Int Ed Engl ; : e202410210, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39023074

RESUMO

Zn metal suffers from severe zinc dendrites, anion-related side reactions, hydrogen evolution reaction (HER) and narrow electrochemical stable window (ESW). Herein, an"anions-in-colloid" hydrated deep eutectic electrolyte (ACDE-3) is designed to improve the stability of zinc anode. The ACDE-3 reconfigures the hydrogen-bond (HB) network and regulates the solvation shell. More importantly, the hydroxyl-rich ß-cyclodextrins (ß-CDs) in ACDE-3 self-assemble into micelles, in which the steric effect between the adjacent ß-CDs restricts the movement of anions. This unique "anions-in-colloid" structure enables the eutectic system with a high Zn2+ transference number (tZn2+) of 0.84.  Thus, ACDE-3 inhibits the formation of dendrite, prevents the anion-involved side reactions, suppresses the HER, and enlarges the ESW to 2.32 V. The Zn//Zn symmetric cell delivers a long lifespan of 900 hours at 0.5 mAh cm-2, and the Zn//Cu half cells have a high average columbic efficiency (ACE) of 97.9% at 0.5 mAh cm-2 with a uniform and compact zinc deposition. When matched with a poly(1,5-naphthalenediamine) cathode, the full battery with a low negative/positive capacity ratio of 2 can still cycle steadily for 200 cycles at a current density of 1.0 A g-1. Additionally, this electrolyte can operative over a wide temperature range from -40 °C to 40 °C.

11.
Front Surg ; 11: 1360982, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966233

RESUMO

Background: Oblique lateral interbody fusion (OLIF) combined with transpedicular screw fixation has been practiced for degenerative spinal diseases of elderly patients for years. However, overweight patients have been shown to have longer operative times and more complications from surgery. The effect on clinical outcome is still uncertified. The objective of this study was to determine is overweight a risk factor to clinical outcome of OLIF combined with transpedicular screw fixation technique. Material and methods: A retrospective study in patients submitted to OLIF combined with transpedicular screw fixation from January 2018 to August 2019 was conducted. VAS score, ODI score and EQ5D were measured before the operation and one year after the operation. Results: A total of 111 patients were included with 48 patients in the non-obese group and 55 patients in the overweight/obese group. There was no significant difference between the two groups in gender, age, smoking history, hypertension, chronic kidney disease and diabetes mellitus. Overweight/obese group has higher BMI (28.4 vs. 22.7, p < 0.001) than non-obese group. There was no difference between the two groups in pre-operative VAS score, ODI score and EQ5D score. However, the healthy weight group improved much more than the overweight score in VAS score, ODI score and EQ5D score. Conclusion: The overweight/obese patient group had clinical outcomes worse than the non-obese group in terms of pain relief and life functions.

12.
World J Diabetes ; 15(6): 1263-1271, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38983812

RESUMO

BACKGROUND: Cognitive dysfunction is the main manifestation of central neuropathy. Although cognitive impairments tend to be overlooked in patients with diabetes mellitus (DM), there is a growing body of evidence linking DM to cognitive dysfunction. Hyperglycemia is closely related to neurological abnormalities, while often disregarded in clinical practice. Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM (T2DM). AIM: To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c (HbA1c) levels. METHODS: A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital. The participants were divided into four groups according to their HbA1c levels using the interquartile method, namely Q1 (< 7.875%), Q2 (7.875%-9.050%), Q3 (9.050%-11.200%) and Q4 (≥ 11.200%). Clinical data were collected and measured, including age, height, weight, neck/waist/hip circumferences, blood pressure, comorbidities, duration of DM, and biochemical indicators. Meanwhile, neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy. RESULTS: The HbA1c level was significantly associated with urinary microalbumin (mALB), triglyceride, low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), and beta cell function (HOMA-ß), N-acetylaspartate/creatine (NAA/Cr), and NAA/choline (NAA/Cho). Spearman correlation analysis showed that mALB, LDL-C, HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c (P < 0.05), whereas HOMA-ß was negatively correlated with the HbA1c level (P < 0.05). Ordered multiple logistic regression analysis showed that NAA/Cho [Odds ratio (OR): 1.608, 95% confidence interval (95%CI): 1.004-2.578, P < 0.05], LDL-C (OR: 1.627, 95%CI: 1.119-2.370, P < 0.05), and HOMA-IR (OR: 1.107, 95%CI: 1.031-1.188, P < 0.01) were independent predictors of poor glycemic control. CONCLUSION: The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control, which may be the basis for the changes in cognitive function in diabetic patients.

13.
Front Immunol ; 15: 1389446, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39034996

RESUMO

Microbiota has been closely related to human beings, whose role in tumor development has also been widely investigated. However, previous studies have mainly focused on the gut, oral, and/or skin microbiota. In recent years, the study of intratumoral microbiota has become a hot topic in tumor-concerning studies. Intratumoral microbiota plays an important role in the occurrence, development, and response to treatment of malignant tumors. In fact, increasing evidence has suggested that intratumoral microbiota is associated with malignant tumors in various ways, such as promoting the tumor development and affecting the efficacy of chemotherapy and immunotherapy. In this review, the impact of intratumoral microbiota on the immune microenvironment of malignant tumors has been analyzed, as well as its role in tumor immunotherapy, with the hope that it may contribute to the development of diagnostic tools and treatments for related tumors in the future.


Assuntos
Imunoterapia , Microbiota , Neoplasias , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/microbiologia , Imunoterapia/métodos , Microbiota/imunologia , Animais
14.
Biochem Biophys Res Commun ; 727: 150336, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38959731

RESUMO

Myocardial fibrosis involves the loss of cardiomyocytes, myocardial fibroblast proliferation, and a reduction in angiogenesis, ultimately leading to heart failure, Given its significant implications, it is crucial to explore novel therapies for myocardial fibrosis. Recently one emerging avenue has been the use of small extracellular vesicles (sEV)-carried miRNA. In this review, we summarize the regulatory role of sEV-carried miRNA in myocardial fibrosis. We explored not only the potential diagnostic value of circulating miRNA as biomarkers for heart disease but also the therapeutic implications of sEV-carried miRNA derived from various cellular sources and applications of modified sEV. This exploration is paramount for researchers striving to develop innovative, cell-free therapies as potential drug candidates for the management of myocardial fibrosis.


Assuntos
Vesículas Extracelulares , Fibrose , MicroRNAs , Humanos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Fibrose/genética , Animais , Miocárdio/patologia , Miocárdio/metabolismo , Cardiomiopatias/genética , Cardiomiopatias/patologia , Cardiomiopatias/metabolismo , Biomarcadores/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia
15.
Pest Manag Sci ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958097

RESUMO

BACKGROUND: Aphid infestation adversely affects the yield and quality of crops. Rapid reproduction and insecticidal resistance have made controlling aphids in the field challenging. Therefore, the present study investigated the insecticidal property of Penicillium oxalicum (QLhf-1) and its mechanism of action against aphids, Hyalopterus arundimis Fabricius. RESULTS: Bioassay revealed that the control efficacy of the spores against aphids (86.30% and 89.05% on the third day and fifth day after infection, respectively) were higher than other components, such as the mycelium. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that QLhf-1 invaded the aphid cuticle through spores and used the aphid tissues as a nutrient source for growth and reproduction, causing stiffness and atrophy and a final death. Three extracellular enzymes, lipase, protease, and chitinase had a synergistic effect with spores, and they acted together to complete the infection process by degrading the aphid body wall and accelerating the infection process. CONCLUSION: The newly discovered endophytic penicillin strain P. oxalicum 'QLhf-1' can effectively kill aphids. The results provided strong evidence for the biological control of aphids, and lay a foundation for the development and utilization of QLhf-1. © 2024 Society of Chemical Industry.

16.
Nat Commun ; 15(1): 5879, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-38997253

RESUMO

The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.


Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Xantenos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Xantenos/síntese química , Xantenos/farmacologia , Xantenos/química , Testes de Sensibilidade Microbiana , Estereoisomerismo , Compostos Policíclicos/síntese química , Compostos Policíclicos/farmacologia , Compostos Policíclicos/química , Descoberta de Drogas , Estrutura Molecular
17.
J Electrocardiol ; 86: 153763, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39079367

RESUMO

Brugada syndrome (BrS) is a rare autosomal dominant inherited channel disorder characterized by a specific electrocardiographic pattern of right precordial ST-segment elevation. Clinically, patients may experience polymorphic ventricular tachycardia and ventricular fibrillation, leading to recurrent syncope and sudden cardiac death (SCD) in the absence of structural cardiomyopathy. The A-kinase anchor protein 9 (AKAP9) gene, located on chromosome 7, encodes the AKAP9 protein, which plays a crucial role in regulating the phosphorylation of slowly activating delayed rectifier potassium channels (IKs). Here, we present a rare case of BrS associated with an insertion mutation in AKAP9, resulting in a frameshift mutation.

19.
Mol Biol Evol ; 41(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38829799

RESUMO

Global climate change has led to shifts in the distribution ranges of many terrestrial species, promoting their migration from lower altitudes or latitudes to higher ones. Meanwhile, successful invaders have developed genetic adaptations enabling the colonization of new environments. Over the past 40 years, Rattus tanezumi (RT) has expanded into northern China (Northwest and North China) from its southern origins. We studied the cold adaptation of RT and its potential for northward expansion by comparing it with sympatric Rattus norvegicus (RN), which is well adapted to cold regions. Through population genomic analysis, we revealed that the invading RT rats have split into three distinct populations: the North, Northwest, and Tibetan populations. The first two populations exhibited high genetic diversity, while the latter population showed remarkably low genetic diversity. These rats have developed various genetic adaptations to cold, arid, hypoxic, and high-UV conditions. Cold acclimation tests revealed divergent thermoregulation between RT and RN. Specifically, RT exhibited higher brown adipose tissue activity and metabolic rates than did RN. Transcriptome analysis highlighted changes in genes regulating triglyceride catabolic processes in RT, including Apoa1 and Apoa4, which were upregulated, under selection and associated with local adaptation. In contrast, RN showed changes in carbohydrate metabolism genes. Despite the cold adaptation of RT, we observed genotypic and phenotypic constraints that may limit its ability to cope with severe low temperatures farther north. Consequently, it is less likely that RT rats will invade and overlap with RN rats in farther northern regions.


Assuntos
Aclimatação , Temperatura Baixa , Animais , Ratos , Aclimatação/genética , China , Fenótipo , Variação Genética , Adaptação Fisiológica/genética , Regulação da Temperatura Corporal/genética , Mudança Climática
20.
Front Immunol ; 15: 1405084, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835771

RESUMO

Introduction: Cynaroside exhibits various biological properties, including anti-inflammatory, antiviral, antitumor, and cardioprotective effects. However, its involvement in methotrexate (MTX)-induced intestinal inflammation remains inadequately understood. Thus, we investigated the impact of cynaroside on MTX-induced intestinal inflammation and its potential mechanisms. Methods: To assess the protective potential of cynaroside against intestinal inflammation, Sprague-Dawley rats were subjected to a regimen of 7 mg/kg MTX for 3 days, followed by treatment with cynaroside at varying doses (10, 20, or 40 mg/kg). Histopathological evaluations were conducted alongside measurements of inflammatory mediators to elucidate the involvement of the NLRP3 inflammasome in alleviating intestinal inflammation. Results: Administration of 7 mg/kg MTX resulted in decreased daily food intake, increased weight loss, and elevated disease activity index in rats. Conversely, treatment with cynaroside at 20 or 40 mg/kg ameliorated the reductions in body weight and daily food intake and suppressed the MTX-induced elevation in the disease activity index. Notably, cynaroside administration at 20 or 40 mg/kg attenuated inflammatory cell infiltration, augmented goblet cell numbers and lowered serum levels of tumor necrosis factor-α, interleukin (IL)-1ß, and IL-18, as well as the CD68-positive cell rate in the intestines of MTX-induced rats. Furthermore, cynaroside downregulated the expression levels of NLRP3, cleaved caspase 1, and cleaved IL-1ß in MTX-induced rats. Discussion: Collectively, our findings indicated that cymaroside alleviates intestinal inflammatory injury by inhibiting the activation of NLRP3 inflammasome in MTX-induced rats.


Assuntos
Enterite , Inflamassomos , Metotrexato , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos Sprague-Dawley , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Ratos , Masculino , Enterite/induzido quimicamente , Enterite/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Citocinas/metabolismo , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Modelos Animais de Doenças
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