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1.
Trials ; 25(1): 431, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956664

RESUMO

BACKGROUND: Use of sedatives and analgesics is associated with the occurrence of delirium in critically ill patients receiving mechanical ventilation. Dexmedetomidine reduces the occurrence of delirium but may cause hypotension, bradycardia, and insufficient sedation. This substudy aims to determine whether the combination of esketamine with dexmedetomidine can reduce the side effects and risk of delirium than dexmedetomidine alone in mechanically ventilated patients. METHODS: This single-center, randomized, active-controlled, superiority trial will be conducted at The First Affiliated Hospital of Nanjing Medical University. A total of 134 mechanically ventilated patients will be recruited and randomized to receive either dexmedetomidine alone or esketamine combined with dexmedetomidine, until extubation or for a maximum of 14 days. The primary outcome is the occurrence of delirium, while the second outcomes include the number of delirium-free days; subtype, severity, and duration of delirium; time to first onset of delirium; total dose of vasopressors and antipsychotics; duration of mechanical ventilation; ICU and hospital length of stay (LOS); accidental extubation, re-intubation, re-admission; and mortality in the ICU at 14 and 28 days. DISCUSSION: There is an urgent need for a new combination regimen of dexmedetomidine due to its evident side effects. The combination of esketamine and dexmedetomidine has been applied throughout the perioperative period. However, there is still a lack of evidence on the effects of this regimen on delirium in mechanically ventilated ICU patients. This substudy will evaluate the effects of the combination of esketamine and dexmedetomidine in reducing the risk of delirium for mechanically ventilated patients in ICU, thus providing evidence of this combination to improve the short-term prognosis. The study protocol has obtained approval from the Medical Ethics Committee (ID: 2022-SR-450). TRIAL REGISTRATION: ClinicalTrials.gov: NCT05466708, registered on 20 July 2022.


Assuntos
Delírio , Dexmedetomidina , Quimioterapia Combinada , Hipnóticos e Sedativos , Unidades de Terapia Intensiva , Ketamina , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial , Humanos , Dexmedetomidina/administração & dosagem , Dexmedetomidina/efeitos adversos , Dexmedetomidina/uso terapêutico , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/uso terapêutico , Delírio/prevenção & controle , Resultado do Tratamento , Tempo de Internação , Estado Terminal , China , Fatores de Tempo , Feminino , Masculino
2.
Heliyon ; 10(12): e33181, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39005927

RESUMO

Trichomonas tenax, an oral commensal parasite commonly found in the human mouth, is associated with periodontitis and poor oral hygiene. However, it has also been identified in the bronchoalveolar lavage fluid (BALF) of individuals with lung diseases. Notably, significant quantities of T. tenax have been isolated following bronchoscopy in cases of empyema and acute respiratory distress syndrome (ARDS). Furthermore, research has demonstrated its ability to induce inflammation in pulmonary epithelial cells. To comprehend the potential role of T. tenax in pneumonia, it is crucial to elucidate the relationship between the parasite and the disease. We investigated the clinical factors associated with T. tenax infection in patients with pneumonia. Employing nested polymerase chain reactions, we amplified nucleic acids from BALF and analyzed the relationships between T. tenax and various clinical factors. Our data revealed a significant association between T. tenax and bacterial infections, high pneumonia severity index (PSI) scores, nasogastric tube feeding, and pulmonary complications. Logistic regression analyses also showed strong associations between T. tenax and these clinical factors in pneumonia patients. These findings suggest that T. tenax infection in pneumonia is accompanied by bacterial infection and severe clinical manifestations.

3.
Angew Chem Int Ed Engl ; : e202412283, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39011879

RESUMO

Circularly polarized electroluminescence (CPEL) is highly promising in realm of 3D display and optical data storage. However, designing a groundbreaking chiral material with high comprehensive CPEL performance remains a formidable challenge. In this work, a pair of chiral polymers with self-assembled behavior is designed by integrating a chiral BN-moiety into polyfluorene backbone, named R-PBN and S-PBN, respectively. The chiral polymers show narrowband emission centered at 490 nm with full-width half maximum (FWHM) of 29 nm and high photoluminescence quantum yield (PLQY) of 79%. After thermal annealing treatment, the chiral polymers undergo self-assembly, exhibiting amplified circularly polarized luminescence (CPL) with asymmetry factor (|glum|) of up to 0.11. Moreover, the solution-processed nondoped CP-OLEDs based on the chiral polymers as emitting layers exhibit maximum external quantum efficiency (EQEmax) of 9.8%, intense CPEL activities with |gEL| of up to 0.07, and small FWHM of 36 nm, simultaneously. This represents the first case of self-assembled chiral polymers that combines high EQE, large gEL value and narrowband emission.

4.
mSphere ; : e0043924, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012105

RESUMO

Companion animals such as cats and dogs harbor diverse microbial communities that can potentially impact human health due to close and frequent contact. To better characterize their total infectomes and assess zoonotic risks, we characterized the overall infectomes of companion animals (cats and dogs) and evaluated their potential zoonotic risks. Meta-transcriptomic analyses were performed on 239 samples from cats and dogs collected across China, identifying 24 viral species, 270 bacterial genera, and two fungal genera. Differences in the overall microbiome and infectome composition were compared across different animal species (cats or dogs), sampling sites (rectal or oropharyngeal), and health status (healthy or diseased). Diversity analyses revealed that viral abundance was generally higher in diseased animals compared to healthy ones, while differences in microbial composition were mainly driven by sampling site, followed by animal species and health status. Disease association analyses validated the pathogenicity of known pathogens and suggested potential pathogenic roles of previously undescribed bacteria and newly discovered viruses. Cross-species transmission analyses identified seven pathogens shared between cats and dogs, such as alphacoronavirus 1, which was detected in both oropharyngeal and rectal swabs albeit with differential pathogenicity. Further analyses showed that some viruses, like alphacoronavirus 1, harbored multiple lineages exhibiting distinct pathogenicity, tissue, or host preferences. Ultimately, a systematic evolutionary screening identified 27 potential zoonotic pathogens in this sample set, with far more bacterial than viral species, implying potential health threats to humans. Overall, our meta-transcriptomic analysis reveals a landscape of actively transcribing microorganisms in major companion animals, highlighting key pathogens, those with the potential for cross-species transmission, and possible zoonotic threats. IMPORTANCE: This study provides a comprehensive characterization of the entire community of infectious microbes (viruses, bacteria, and fungi) in companion animals like cats and dogs, termed the "infectome." By analyzing hundreds of samples from across China, the researchers identified numerous known and novel pathogens, including 27 potential zoonotic agents that could pose health risks to both animals and humans. Notably, some of these zoonotic pathogens were detected even in apparently healthy pets, highlighting the importance of surveillance. The study also revealed key microbial factors associated with respiratory and gastrointestinal diseases in pets, as well as potential cross-species transmission events between cats and dogs. Overall, this work sheds light on the complex microbial landscapes of companion animals and their potential impacts on animal and human health, underscoring the need for monitoring and management of these infectious agents.

5.
Int J Surg ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38959093

RESUMO

INTRODUCTION: The influence of deranged body composition on stage I/II HCC after surgery remains undetermined. The current study aimed to investigate the impact of low skeletal muscle bulk and disturbed body fat mass on the recurrence outcome of stage I/II HCC patients undergoing liver resection. The associated metabolomic alterations were also assessed. METHODS: From 2012 to 2021, stage I and II HCC patients who underwent liver resection at our institute were retrospectively reviewed. Their preoperative body composition including skeletal muscle mass and body fat volume was measured by computed tomography (CT). The recurrence outcome was recorded and analyzed. The preoperative serum was collected and subjected to metabolomic analysis. RESULTS: A total of 450 stage I and II HCC patients were included in the current study. Among them, 76% were male and around 60% had HBV infection. After stratified by normal cutoff values obtained from a healthy cohort, 6.4% of stage I/II HCC patients were found to have a low psoas muscle index (PMI), 17.8% a high subcutaneous adipose tissue (SAT) index, and 27.8% a high visceral adipose tissue (VAT) index. Cox regression multivariate analysis further demonstrated that low PMI and high SAT index were independent prognostic factors for time-to-recurrence (TTR) after surgery. Metabolomic analysis discovered that free fatty acid ß-oxidation was enhanced in with low PMI or high SAT index. CONCLUSION: The current study demonstrated that reduced psoas muscle mass may impair while elevated SAT may prolong the TTR of stage I/II HCC patients undergoing liver resections. VAT, on the other hand, was not associated with recurrence outcome after surgery. Further studies are warranted to validate our findings.

6.
J Med Internet Res ; 26: e49530, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963936

RESUMO

BACKGROUND: Circadian rhythm disruptions are a common concern for poststroke patients undergoing rehabilitation and might negatively impact their functional outcomes. OBJECTIVE: Our research aimed to uncover unique patterns and disruptions specific to poststroke rehabilitation patients and identify potential differences in specific rest-activity rhythm indicators when compared to inpatient controls with non-brain-related lesions, such as patients with spinal cord injuries. METHODS: We obtained a 7-day recording with a wearable actigraphy device from 25 poststroke patients (n=9, 36% women; median age 56, IQR 46-71) and 25 age- and gender-matched inpatient control participants (n=15, 60% women; median age 57, IQR 46.5-68.5). To assess circadian rhythm, we used a nonparametric method to calculate key rest-activity rhythm indicators-relative amplitude, interdaily stability, and intradaily variability. Relative amplitude, quantifying rest-activity rhythm amplitude while considering daily variations and unbalanced amplitudes, was calculated as the ratio of the difference between the most active 10 continuous hours and the least active 5 continuous hours to the sum of these 10 and 5 continuous hours. We also examined the clinical correlations between rest-activity rhythm indicators and delirium screening tools, such as the 4 A's Test and the Barthel Index, which assess delirium and activities of daily living. RESULTS: Patients who had a stroke had higher least active 5-hour values compared to the control group (median 4.29, IQR 2.88-6.49 vs median 1.84, IQR 0.67-4.34; P=.008). The most active 10-hour values showed no significant differences between the groups (stroke group: median 38.92, IQR 14.60-40.87; control group: median 31.18, IQR 18.02-46.84; P=.93). The stroke group presented a lower relative amplitude compared to the control group (median 0.74, IQR 0.57-0.85 vs median 0.88, IQR 0.71-0.96; P=.009). Further analysis revealed no significant differences in other rest-activity rhythm metrics between the two groups. Among the patients who had a stroke, a negative correlation was observed between the 4 A's Test scores and relative amplitude (ρ=-0.41; P=.045). Across all participants, positive correlations emerged between the Barthel Index scores and both interdaily stability (ρ=0.34; P=.02) and the most active 10-hour value (ρ=0.42; P=.002). CONCLUSIONS: This study highlights the relevance of circadian rhythm disruptions in poststroke rehabilitation and provides insights into potential diagnostic and prognostic implications for rest-activity rhythm indicators as digital biomarkers.


Assuntos
Ritmo Circadiano , Descanso , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/complicações , Ritmo Circadiano/fisiologia , Actigrafia/métodos , Estudos de Casos e Controles
7.
Mol Psychiatry ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971895

RESUMO

Previous studies have shown an association between the thalamocortical dysconnectivity and treatment-resistant depression (TRD). Whether a single subanesthetic dose of ketamine may change thalamocortical connectivity among patients with TRD is unclear. Whether these changes in thalamocortical connectivity is associated with the antidepressant and antisuicidal effects of ketamine treatment is also unclear. Two resting-state functional MRIs were collected in two clinical trials of 48 patients with TRD (clinical trial 1; 32 receiving ketamine, 16 receiving a normal saline placebo) and 48 patients with TRD and strong suicidal ideation (clinical trial 2; 24 receiving ketamine, 24 receiving midazolam), respectively. All participants underwent rs-fMRI before and 3 days after infusion. Seed-based functional connectivity (FC) was analyzed in the left/right thalamus. FCs between the bilateral thalamus and right middle frontal cortex (BA46) and between the left thalamus and left anterior paracingulate gyrus (BA8) increased among patients in the ketamine group in clinical trials 1 and 2, respectively. FCs between the right thalamus and bilateral frontal pole (BA9) and between the right thalamus and left rostral paracingulate gyrus (BA10) decreased among patients in the ketamine group in clinical trials 1 and 2, respectively. However, the associations between those FC changes and clinical symptom changes did not survive statistical significance after multiple comparison corrections. Whether ketamine-related changes in thalamocortical connectivity may be associated with ketamine's antidepressant and antisuicidal effects would need further investigation. Clinical trials registration: UMIN Clinical Trials Registry (UMIN-CTR): Registration number: UMIN000016985 and UMIN000033916.

8.
Clin Biochem ; 129: 110779, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38871043

RESUMO

The Hospital at Home (HaH) program has experienced accelerated growth in major Canadian provinces, driven in part by technological advancements and evolving patient needs during the COVID-19 pandemic. As an increasing number of hospitals pilot or implement these innovative programs, substantial resources have been allocated to support clinical teams. However, it is crucial to note that the vital roles played by clinical laboratories remain insufficiently acknowledged. This mini review aims to shed light on the diverse functions of clinical laboratories, spanning the preanalytical, analytical, and post-analytical phases within the HaH program context. Additionally, the review will explore recent advancements in clinical testing and the potential benefits of integrating new technologies into the HaH framework. Emphasizing the integral role of clinical laboratories, the discussion will address the current barriers hindering their active involvement, accompanied by proposed solutions. The capacity and efficiency of the HaH program hinge on sustained collaborative efforts from various teams, with clinical laboratories as crucial team players. Recognizing and addressing the specific challenges faced by clinical laboratories is essential for optimizing the overall performance and impact of the HaH initiative.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Canadá , SARS-CoV-2 , Pandemias , Laboratórios Clínicos , Serviços Hospitalares de Assistência Domiciliar/organização & administração , Pacientes Internados
9.
Animals (Basel) ; 14(12)2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38929373

RESUMO

In this study, six different animal models were fitted, and the constrained maximum likelihood method was used to assess the genetic parameters and genetic trends of early growth traits in Luzhong mutton sheep. The experimental data of this study included the newborn weight (BWT, N = 2464), weaning weight (WWT, N = 2923), weight at 6 months of age (6WT, N = 2428), average daily weight gain from birth to weaning (ADG1, N = 2424), and average daily weight gain from weaning to 6 months of age (ADG2, N = 1836) in Luzhong mutton sheep (2015~2019). The best model for the genetic parameters of the five traits in Luzhong mutton sheep was identified as Model 4 using the Akaike information criterion (AIC) and likelihood ratio test (LRT) methods, in which the estimated values of direct heritability for the BWT, WWT, 6WT, ADG1, and ADG2 were 0.156 ± 0.057, 0.547 ± 0.031, 0.653 ± 0.031, 0.531 ± 0.035, and 0.052 ± 0.046, respectively, and the values for maternal heritability were 0.201 ± 0.100, 0.280 ± 0.047, 0.197 ± 0.053, 0.275 ± 0.052, and 0.081 ± 0.092, respectively. The genetic correlation between the ADG2 and WWT was negative, and the genetic and phenotypic correlations among the remaining traits were positive. In this study, maternal effects had a more significant influence on early growth traits in Luzhong mutton sheep. In conclusion, to effectively improve the accuracy of genetic parameter estimation, maternal effects must be fully considered to ensure more accurate and better breeding planning.

11.
J Brachial Plex Peripher Nerve Inj ; 19(1): e20-e26, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38868462

RESUMO

Background With the advent of the coronavirus disease 2019 (COVID-19) pandemic, some doubts have been raised regarding the potential respiratory problems that patients who previously underwent a phrenic nerve transfer could have. Objectives To analyze the effects of the coronavirus infection on two populations, one from Argentina and another from Taiwan. Specific objectives were: (1) to identify the rate of COVID in patients with a history of phrenic nerve transfer for treatment of palsy; (2) to identify the overall symptom profile; (3) to compare Argentinian versus Taiwanese populations; and (4) to determine if any phrenic nerve transfer patients are at particular risk of more severe COVID. Methods A telephonic survey that included data regarding the number of episodes of acute COVID-19 infection, the symptoms it caused, the presence or absence of potential or life-threatening complications, and the status of COVID-19 vaccination were studied. Intergroup comparisons were conducted using the nonparametric Mann-Whitney U test, with categorical variables conducted using either the Pearson χ2 analysis or the Fisher's exact test, as appropriate. Results A total of 77 patients completed the survey, 40 from Taiwan and 37 from Argentina. Fifty-five (71.4%) developed a diagnosis of COVID. However, among these, only four had any level of dyspnea reported (4/55 = 7.3%), all mild. There were also no admissions to hospital or an intensive care unit, no intubations, and no deaths. All 55 patients isolated themselves at home. Conclusions It can be concluded that an acute COVID-19 infection was very well tolerated in our patients. (Level of evidence 3b, case reports).

12.
Opt Express ; 32(10): 17165-17172, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38858906

RESUMO

We propose what we believe to be a new single-beam three-axis spin exchange relaxation free (SERF) vector atomic magnetometer scheme based on coordinate system deflection. A theoretical model for the system response under arbitrary angle deflection was established for the first time, and the system response at different angles was simulated and analyzed. The simulation results show that the system response increases in the direction of the non-sensitive axis and decreases in the direction of the sensitive axis as the deflection angle increases, and the two responses tend to be the same when the angle is deflected to 45-degrees. Experimental measurements were carried out at a deflection angle of 45-degrees and the results showed that the sensitivity of the magnetometer was 55fT/Hz1/2 in the x1-axis, 38fT/Hz1/2 in the y1-axis and 60fT/Hz1/2 in the z1-axis. This single-beam magnetometer can be used to construct a miniaturized and low-cost weak magnetic sensor, which is expected to be used for vector measurement of biomagnetism.

13.
Biomed J ; : 100757, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38942384

RESUMO

Liver transplantation (LT) is considered the ideal treatment for hepatocellular carcinoma (HCC) concurrent with underlying cirrhotic liver disease. As well-known, LT for HCC based on the Milan criteria has shown satisfactory outcomes. However, numerous expanded transplantation criteria were proposed to benefit more patients for LT and showed comparable survivals as well. In addition, a modest expansion of transplantation criteria for HCC may be acceptable on the basis of the consensus within the transplantation community. Nonetheless, LT in patients with advanced HCC and portal vein tumor thrombosis (PVTT) recently has received attention and has been reported by many transplantation centers despite being contraindicated. Of those, the LT outcomes in certain HCC patients with PVTT were favorable. Additionally, the advancement of multimodality treatments and the evolution of systemic therapies have emerged as promising therapeutic options for downstaging advanced HCC prior to LT. Somehow, advanced HCC with PVTT could be downstaged to become eligible for LT through these multidisciplinary approaches. Although the available evidence of LT for HCC with PVTT is limited, it is hoped that LT may soon be more widely indicated for these patients. Nevertheless, several unknown factors associated with LT for HCC remain to be explored. Herein, this review aimed to update the developments in LT for patients with advanced HCC.

14.
J Am Soc Mass Spectrom ; 35(7): 1507-1515, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38905484

RESUMO

Over the past decades, proteomics has become increasingly important and a heavily discussed topic. The identification of intact proteins remains a major focus in this field. While most intact proteins are analyzed using high-resolution mass spectrometry, identifying them through low-resolution mass spectrometry continues to pose challenges. In our study, we investigated the capability of identifying various intact proteins using collision-induced dissociation (CID) and electron transfer without dissociation (ETnoD). Using myoglobin as our test protein, stable product ions were generated with CID, and the identities of the product ions were identified with ETnoD. ETnoD uses a short activation time (AcT, 5 ms) to create sequential charge-reduced precursor ion (CRI). The charges of the fragments and their sequences were determined with corresponding CRI. The product ions can be selected for subsequent CID (termed CIDn) combined with ETnoD for further sequence identification and validation. We refer to this method as CIDn/ETnoD. The use of a multistage CID activation (CIDn) and ETnoD protocol has been applied to several intact proteins to obtain multiple sequence identifications.


Assuntos
Mioglobina , Proteômica , Mioglobina/química , Mioglobina/análise , Proteômica/métodos , Animais , Proteínas/química , Proteínas/análise , Sequência de Aminoácidos , Cavalos , Espectrometria de Massas/métodos , Dados de Sequência Molecular , Espectrometria de Massas em Tandem/métodos
15.
ACS Catal ; 14(7): 4975-4983, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38895101

RESUMO

A number of bacteria are known to produce isonitrile-containing peptides (INPs) that facilitate metal transport and are important for cell survival; however, considerable structural variation is observed among INPs depending on the producing organism. While non-heme iron 2-oxoglutarate dependent isonitrilases catalyze isonitrile formation, how the natural variation in INP structure is controlled and its implications for INP bioactivity remain open questions. Herein, total chemical synthesis is utilized with X-Ray crystallographic analysis of mycobacterial isonitrilases to provide a structural model of substrate specificity that explains the longer alkyl chains observed in mycobacterial versus Streptomyces INPs. Moreover, proton NMR titration experiments demonstrate that INPs regardless of alkyl chain length are specific for binding copper instead of zinc. These results suggest that isonitrilases may act as gatekeepers in modulating the observed biological distribution of INP structures and this distribution may be primarily related to differing metal transport requirements among the producing strains.

16.
Chembiochem ; : e202400307, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900645

RESUMO

Non-heme mononuclear iron dependent (NHM-Fe) enzymes exhibit exceedingly diverse catalytic reactivities. Despite their catalytic versatilities, the mononuclear iron centers in these enzymes show a relatively simple architecture, in which an iron atom is ligated with 2-4 amino acid residues, including histidine, aspartic or glutamic acid. In the past two decades, a common high-valent reactive iron intermediate, the S = 2 oxoferryl (Fe(IV)-oxo or Fe(IV)=O) species, has been repeatedly discovered in NHM-Fe enzymes containing a 2-His-Fe or 2-His-1-carboxylate-Fe center. However, for 3-His/4-His-Fe enzymes, no common reactive intermediate has been identified. Recently, we have spectroscopically characterized the first S = 1 Fe(IV) intermediate in a 3-His-Fe containing enzyme, OvoA, which catalyzes a novel oxidative carbon-sulfur bond formation. In this review, we summarize the broad reactivities demonstrated by S = 2 Fe(IV)-oxo intermediates, the discovery of the first S = 1 Fe(IV) intermediate in OvoA and the mechanistic implication of such a discovery, and the intrinsic reactivity differences of the S = 2 and the S = 1 Fe(IV)-oxo species. Finally, we postulate the possible reasons to utilize an S = 1 Fe(IV) species in OvoA and their implications to other 3-His/4-His-Fe enzymes.

17.
Iran J Allergy Asthma Immunol ; 23(2): 211-219, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38822515

RESUMO

Asthma is a chronic respiratory disease that is characterized by airway inflammation, excessive mucus production, and airway remodeling. Prevention and treatment for asthma is an urgent issue in clinical studies. In recent years, N6-methyladenosine methylation (m6A) has emerged as a promising regulatory approach involved in multiple diseases. ALKBH5 (alkB homolog 5) is a demethylase widely studied in disease pathologies. This work aimed to explore the regulatory mechanisms underlying the ALKBH5-regulated asthma. We established an interleukin-13 (IL-13)-stimulated cell model to mimic the in vitro inflammatory environment of asthma. ALKBH5 knockdown in bronchial epithelial cells was performed using siRNAs, and the knockdown efficacy was analyzed by quantitative PCR (qPCR). Cell viability and proliferation were measured by cell counting kit 8 (CCK-8) and colony formation assay. The ferroptosis was assessed by measuring the total iron, Fe2+, lipid reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) levels. The enrichment of N6-methyladenosine methylation (m6A) modification was detected by the MeRIP assay. Knockdown of ALKBH5 significantly elevated the survival and colony formation ability of bronchial epithelial cells in the IL-13 induction model. The levels of total iron, Fe2+, lipid ROS, and MDA were remarkedly elevated, and the SOD level was reduced in IL-13-induced bronchial epithelial cells, and depletion of ALKBH5 reversed these effects. Knockdown of ALKBH5 elevated the enrichment of m6A modification and expression of glutathione peroxidase 4 (GPX4). Knockdown of GPX4 abolished the pro-proliferation and anti-ferroptosis effects of siALKBH5. Knockdown of ALKBH5 improved the proliferation of bronchial epithelial cells and alleviated cell ferroptosis.


Assuntos
Adenosina , Homólogo AlkB 5 da RNA Desmetilase , Asma , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/genética , Asma/genética , Asma/metabolismo , Asma/patologia , Humanos , Adenosina/análogos & derivados , Adenosina/metabolismo , Proliferação de Células/genética , Metilação , Progressão da Doença , Linhagem Celular , Ferroptose/genética , Células Epiteliais/metabolismo , Regulação para Baixo , Brônquios/patologia , Brônquios/metabolismo , Técnicas de Silenciamento de Genes , Sobrevivência Celular/genética
18.
Reprod Domest Anim ; 59(6): e14598, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38881434

RESUMO

Our previous research has shown that melatonin (MLT) can reduce cryopreserved ovarian damage in mice. Yet, the molecular mechanism of MLT protection is still unclear. Some studies have shown that melatonin receptor 1 (MT1) is very important for animal reproductive system. To evaluate whether MLT exerts its protective effect on cryopreserved mice ovarian tissue via MT1, we added antagonist of MT1/MT2 (Luzindor) or antagonist of MT2 (4P-PDOT) to the freezing solution, followed by cryopreservation and thawing of ovarian tissue. The levels of total superoxide dismutase (T-SOD), catalase (CAT), nitric oxide (NO) and malondialdehyde (MDA) were detected. Besides, by using RT-PCR and Western blotting, the expression of Bcl-2, Bax and Nrf2/HO-1 signalling pathway-related proteins was detected. These findings demonstrated that compared with the melatonin group, the addition of Luzindor increased apoptosis, NO and MDA activities, decreased CAT and T-SOD activities and inhibited Nrf2/HO-1 signalling pathway. In conclusion, melatonin can play a protective role in cryopreserved ovarian tissue of mice through MT1 receptor.


Assuntos
Criopreservação , Melatonina , Fator 2 Relacionado a NF-E2 , Ovário , Estresse Oxidativo , Receptor MT1 de Melatonina , Transdução de Sinais , Animais , Feminino , Melatonina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ovário/efeitos dos fármacos , Receptor MT1 de Melatonina/metabolismo , Receptor MT1 de Melatonina/genética , Transdução de Sinais/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Camundongos , Criopreservação/veterinária , Triptaminas/farmacologia , Apoptose/efeitos dos fármacos , Heme Oxigenase (Desciclizante)/metabolismo , Heme Oxigenase (Desciclizante)/genética , Óxido Nítrico/metabolismo , Malondialdeído/metabolismo , Proteínas de Membrana , Heme Oxigenase-1
19.
Angew Chem Int Ed Engl ; : e202409020, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899789

RESUMO

The strategy of integrating conformational isomerization donors and chiral acceptor in single molecule was proposed to construct white circularly polarized luminescence (WCPL) materials in this work. Consequently, a pair of dual-emission enantiomers, namely (R/S)-DO-PTZ, were designed and synthesized, which displayed white emission with blue and yellow dual-emission bands in solution and solid films at Commission Internationale de l'Eclairage (CIE) coordinates of (0.30, 0.33) and (0.33, 0.35), respectively. Meanwhile, (R/S)-DO-PTZ exhibited high PLQY of up to 67% in doped films and obvious mirror-image WCPL signals with |glum| value of 3.0 × 10-3. Moreover, white circularly polarized electroluminescence (WCPEL) based on organic light-emitting diodes (OLEDs) with (R/S)-DO-PTZ as emitters were also achieved with CIE coordinates of (0.32, 0.37) and EQEmax of 4.7%, representing the state-of-the-art level of white OLEDs based on single-molecule purely organic emitters. By optimizing the device structure, warm WCPEL devices were further obtained with |gEL| value of 2.8 × 10-3, CIE coordinates of (0.37, 0.48) and EQEmax of up to 15.6%. To our knowledge, this is the first report of CP-WOLEDs based on single-molecule purely organic emitters.

20.
Dig Dis Sci ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824258

RESUMO

BACKGROUND: In many Asian hepatocellular carcinoma (HCC) guidelines, resection is an option for multiple HCCs. It is difficult to compare small but multiple tumors vs. fewer large tumors in terms of the traditional tumor burden definition. We aimed to evaluate the role of liver resection for multiple HCCs and determine factors associated with survival benefits. METHODS: We reviewed 160 patients with multiple HCCs who underwent liver resection between July 2003 and December 2018. The risk factors for tumor recurrence were assessed using Cox proportional hazards modeling, and survival was analyzed using the Kaplan-Meier method. RESULTS: In all 160 patients, 133 (83.1%) exceeded the Milan criteria. Total tumor volume (TTV) > 275 cm3 and serum alpha-fetoprotein (AFP) level > 20 ng/mL were associated with disease-free survival. Patients beyond the Milan criteria were grouped into three risk categories: no risk (TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL, n = 39), one risk (either TTV > 275 cm3 or AFP > 20 ng/mL, n = 76), and two risks (TTV > 275 cm3 and AFP > 20 ng/mL, n = 18). No-risk group had comparable disease-free survival (p = 0.269) and overall survival (p = 0.215) to patients who met the Milan criteria. CONCLUSION: Patients with TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL can have good outcomes even exceed the Milan criteria.

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