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1.
Acta Trop ; : 107318, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39002738

RESUMO

BACKGROUND: Hepatitis B virus (HBV) exhibits high prevalence rates within Ethiopia. The genetic diversity of HBV, marked by mixed genotype infections, may hold significant implications for the trajectory of disease and responses to treatment. Ethiopia grapples with a substantial public health challenge posed by co-infections involving HBV, hepatitis C virus (HCV), and human immunodeficiency virus 1 (HIV-1), particularly among vulnerable populations. METHODS: A comprehensive investigation into HBV, HCV, and HIV-1 co-infection was conducted. A total of 7,789 blood samples were meticulously analyzed, among which 815 exhibited HBV positivity. Among the HBV-positive samples, 630 were subjected to genotyping procedures, resulting in the identification of a prevalent trend of mixed infections characterized by HBV genotypes A/E/F (67.30%). Serological assessments were performed on 492 specimens to ascertain the presence of HCV and HIV-1 co-infections, revealing respective co-infection rates of 13.02% for HBV/HIV, 3.31% for HBV/HCV, and 2.07% for triple infection. RESULTS: The investigation revealed the intricate prevalence of co-infections in Ethiopia, notably underlining the continued transmission of viruses. The prominent occurrence of mixed HBV genotypes A/E/F suggests dynamic viral interactions and ongoing transmission pathways. These findings accentuate the necessity for targeted interventions and enhanced patient care, as co-infections carry significant clinical complexities. CONCLUSIONS: This study furnishes crucial insights into the molecular epidemiology of HBV, HCV, and HIV-1 co-infections in Ethiopia. The acquired knowledge can contribute to the advancement of strategies for clinical management and the formulation of public health interventions aimed at ameliorating the burden of viral infections within the nation.

2.
MycoKeys ; 106: 117-132, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948914

RESUMO

The rotting wood in freshwater is a unique eco-environment favoring various fungi. During our investigation of freshwater fungi on decaying wood, three hyphomycetes were collected from Jiangxi and Guangxi Provinces, China. Based on the morphological observations and phylogenetic analysis of a combined DNA data containing ITS, LSU, SSU and tef1-α sequences, two new Trichobotrys species, T.meilingensis and T.yunjushanensis, as well as a new record of T.effusa, were introduced. Additionally, a comprehensive description of the genus with both morphological and molecular data was first provided.

3.
Dalton Trans ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38952336

RESUMO

The development of heteroatom dual-doped porous carbon frameworks with uniform doping is highly desirable for achieving highly efficient oxygen reduction reaction (ORR) activity, due to their tunable chemical and electronic structures. Herein, porous covalent triazine-based frameworks (CTFs) incorporating nitrogen/chorine dual-doped porous carbon networks were fabricated by selecting 1,3-bis(4-cyanophenyl) imidazolium chloride as a building block, in a facile and controllable way via a bottom-up strategy. The resulting nitrogen/chorine dual-doped catalyst CCTF-700 exhibits excellent ORR performance with a more positive onset and half-wave potential (0.85 V vs. RHE), higher diffusion-limited current density and significantly improved stability in comparison with the benchmark commercial 20 wt% Pt/C catalyst. It is worth mentioning that CCTF-700 shows one of the best ORR performances among all the reported metal-free electrocatalysts under alkaline conditions. This work paves the way for a controllable and reliable strategy to craft highly efficient heteroatom dual-doped carbon catalysts for energy conversion.

4.
World J Clin Cases ; 12(18): 3555-3560, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38983424

RESUMO

BACKGROUND: In recent years, immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy across diverse malignancies. Notably, in patients with advanced gastric cancer, the use of programmed death 1 (PD-1) blockade has significantly prolonged overall survival, marking a pivotal advancement comparable to the impact of Herceptin over the past two decades. While the therapeutic benefits of ICIs are evident, the increasing use of immunotherapy has led to an increase in immune-related adverse events. CASE SUMMARY: This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis. Following sintilimab therapy, the patient developed severe rashes accompanied by cytokine release syndrome (CRS). Fortunately, effective management was achieved through the administration of glucocorticoid, tocilizumab, and acitretin, which resulted in favorable outcomes. CONCLUSION: Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.

5.
J Am Chem Soc ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39011931

RESUMO

Scarce and expensive iridium oxide is still the cornerstone catalyst of polymer-electrolyte membrane electrolyzers for green hydrogen production because of its exceptional stability under industrially relevant oxygen evolution reaction (OER) conditions. Earth-abundant transition metal oxides used for this task, however, show poor long-term stability. We demonstrate here the use of nitrogen-doped cobalt oxide as an effective iridium substitute. The catalyst exhibits a low overpotential of 240 mV at 10 mA cm-2 and negligible activity decay after 1000 h of operation in an alkaline electrolyte. Incorporation of nitrogen dopants not only triggers the OER mechanism switched from the traditional adsorbate evolution route to the lattice oxygen oxidation route but also achieves oxygen nonbonding (ONB) states as electron donors, thereby preventing structural destabilization. In a practical anion-exchange membrane water electrolyzer, this catalyst at anode delivers a current density of 1000 mA cm-2 at 1.78 V and an electrical efficiency of 47.8 kW-hours per kilogram hydrogen.

6.
J Am Heart Assoc ; 13(14): e033232, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38958128

RESUMO

BACKGROUND: Thoracic aortic aneurysm (TAA) is associated with significant morbidity and mortality. Although individuals with family histories of TAA often undergo clinical molecular genetic testing, adults with nonsyndromic TAA are not typically evaluated for genetic causes. We sought to understand the genetic contribution of both germline and somatic mosaic variants in a cohort of adult individuals with nonsyndromic TAA at a single center. METHODS AND RESULTS: One hundred eighty-one consecutive patients <60 years who presented with nonsyndromic TAA at the Massachusetts General Hospital underwent deep (>500×) targeted sequencing across 114 candidate genes associated with TAA and its related functional pathways. Samples from 354 age- and sex-matched individuals without TAA were also sequenced, with a 2:1 matching. We found significant enrichments for germline (odds ratio [OR], 2.44, P=4.6×10-6 [95% CI, 1.67-3.58]) and also somatic mosaic variants (OR, 4.71, P=0.026 [95% CI, 1.20-18.43]) between individuals with and without TAA. Likely genetic causes were present in 24% with nonsyndromic TAA, of which 21% arose from germline variants and 3% from somatic mosaic alleles. The 3 most frequently mutated genes in our cohort were FLNA (encoding Filamin A), NOTCH3 (encoding Notch receptor 3), and FBN1 (encoding Fibrillin-1). There was increased frequency of both missense and loss of function variants in TAA individuals. CONCLUSIONS: Likely contributory dominant acting genetic variants were found in almost one quarter of nonsyndromic adults with TAA. Our findings suggest a more extensive genetic architecture to TAA than expected and that genetic testing may improve the care and clinical management of adults with nonsyndromic TAA.


Assuntos
Aneurisma da Aorta Torácica , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Mosaicismo , Humanos , Masculino , Feminino , Aneurisma da Aorta Torácica/genética , Aneurisma da Aorta Torácica/diagnóstico , Adulto , Pessoa de Meia-Idade , Receptor Notch3/genética , Fibrilina-1/genética , Estudos de Casos e Controles , Fenótipo , Filaminas/genética , Fatores de Risco , Sequenciamento de Nucleotídeos em Larga Escala , Adipocinas
7.
Brain Behav ; 14(7): e3605, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38956819

RESUMO

BACKGROUND: High-frequency repeated transcranial magnetic stimulation (rTMS) stimulating the primary motor cortex (M1) is an alternative, adjunctive therapy for improving the motor symptoms of Parkinson's disease (PD). However, whether the high frequency of rTMS positively correlates to the improvement of motor symptoms of PD is still undecided. By controlling for other parameters, a disease animal model may be useful to compare the neuroprotective effects of different high frequencies of rTMS. OBJECTIVE: The current exploratory study was designed to compare the protective effects of four common high frequencies of rTMS (5, 10, 15, and 20 Hz) and iTBS (a special form of high-frequency rTMS) and explore the optimal high-frequency rTMS on an animal PD model. METHODS: Following high frequencies of rTMS application (twice a week for 5 weeks) in a MPTP/probenecid-induced chronic PD model, the effects of the five protocols on motor behavior as well as dopaminergic neuron degeneration levels were identified. The underlying molecular mechanisms were further explored. RESULTS: We found that all the high frequencies of rTMS had protective effects on the motor functions of PD models to varying degrees. Among them, the 10, 15, and 20 Hz rTMS interventions induced comparable preservation of motor function through the protection of nigrostriatal dopamine neurons. The enhancement of brain-derived neurotrophic factor (BDNF), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT-2) and the suppression of TNF-α and IL-1ß in the nigrostriatum were involved in the process. The efficacy of iTBS was inferior to that of the above three protocols. The effect of 5 Hz rTMS protocol was weakest. CONCLUSIONS: Combined with the results of the present study and the possible side effects induced by rTMS, we concluded that 10 Hz might be the optimal stimulation frequency for preserving the motor functions of PD models using rTMS treatment.


Assuntos
Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Transtornos Parkinsonianos , Probenecid , Estimulação Magnética Transcraniana , Animais , Estimulação Magnética Transcraniana/métodos , Camundongos , Masculino , Probenecid/farmacologia , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/terapia , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Córtex Motor/metabolismo , Córtex Motor/fisiopatologia , Neurônios Dopaminérgicos/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Interleucina-1beta/metabolismo , Substância Negra/metabolismo , Corpo Estriado/metabolismo , Proteínas Vesiculares de Transporte de Monoamina/metabolismo , Intoxicação por MPTP/terapia , Intoxicação por MPTP/prevenção & controle , Intoxicação por MPTP/metabolismo , Intoxicação por MPTP/fisiopatologia , Atividade Motora/fisiologia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia
8.
Materials (Basel) ; 17(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38998224

RESUMO

This study explores the integration of machine learning (ML) techniques to predict and optimize the compressive strength of alkali-activated materials (AAMs) sourced from four industrial waste streams: blast furnace slag, fly ash, reducing slag, and waste glass. Aimed at mitigating the labor-intensive trial-and-error method in AAM formulation, ML models can predict the compressive strength and then streamline the mixture compositions. By leveraging a dataset of only 42 samples, the Random Forest (RF) model underwent fivefold cross-validation to ensure reliability. Despite challenges posed by the limited datasets, meticulous data processing steps facilitated the identification of pivotal features that influence compressive strength. Substantial enhancement in predicting compressive strength was achieved with the RF model, improving the model accuracy from 0.05 to 0.62. Experimental validation further confirmed the ML model's efficacy, as the formulations ultimately achieved the desired strength threshold, with a significant 59.65% improvement over the initial experiments. Additionally, the fact that the recommended formulations using ML methods only required about 5 min underscores the transformative potential of ML in reshaping AAM design paradigms and expediting the development process.

9.
JMIR Mhealth Uhealth ; 12: e53652, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39024567

RESUMO

BACKGROUND:  Cancer pain remains highly prevalent and persistent throughout survivorship, and it is crucial to investigate the potential of leveraging the advanced features of mobile health (mHealth) apps to empower individuals to self-manage their pain. OBJECTIVE:  This review aims to comprehensively understand the acceptability, users' experiences, and effectiveness of mHealth apps in supporting cancer pain self-management. METHODS:  We conducted an integrative review following Souza and Whittemore and Knafl's 6 review processes. Literature was searched in PubMed, Scopus, CINAHL Plus with Full Text, PsycINFO, and Embase, from 2013 to 2023. Keywords including "cancer patients," "pain," "self-management," "mHealth applications," and relevant synonyms were used in the search. The Johns Hopkins research evidence appraisal tool was used to evaluate the quality of eligible studies. A narrative synthesis was conducted to analyze the extracted data. RESULTS:  A total of 20 studies were included, with the overall quality rated as high (n=15) to good (n=5). Using mHealth apps to monitor and manage pain was acceptable for most patients with cancer. The internal consistency of the mHealth in measuring pain was 0.96. The reported daily assessment or engagement rate ranged from 61.9% to 76.8%. All mHealth apps were designed for multimodal interventions. Participants generally had positive experiences using pain apps, rating them as enjoyable and user-friendly. In addition, 6 studies reported significant improvements in health outcomes, including enhancement in pain remission (severity and intensity), medication adherence, and a reduced frequency of breakthrough pain. The most frequently highlighted roles of mHealth apps included pain monitoring, tracking, reminders, education facilitation, and support coordination. CONCLUSIONS:  mHealth apps are effective and acceptable in supporting pain self-management. They offer a promising multi-model approach for patients to monitor, track, and manage their pain. These findings provide evidence-based insights for leveraging mHealth apps to support cancer pain self-management. More high-quality studies are needed to examine the effectiveness of digital technology-based interventions for cancer pain self-management and to identify the facilitators and barriers to their implementation in real-world practice.


Assuntos
Dor do Câncer , Aplicativos Móveis , Autogestão , Telemedicina , Humanos , Dor do Câncer/terapia , Dor do Câncer/psicologia , Autogestão/métodos , Autogestão/psicologia , Telemedicina/normas , Aplicativos Móveis/normas , Aplicativos Móveis/estatística & dados numéricos , Aplicativos Móveis/tendências , Manejo da Dor/métodos , Manejo da Dor/normas , Neoplasias/complicações , Neoplasias/psicologia , Neoplasias/terapia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia
11.
Eur Urol Oncol ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38960834

RESUMO

BACKGROUND AND OBJECTIVE: We investigated the association of clinical factors at presentation with the presence of unsampled high-risk prostate cancer (PC) and PC-specific mortality (PCSM) and all-cause mortality (ACM) following radical prostatectomy in patients with biopsy Gleason Grade Group (GGG) 1 PC. METHODS: The study population comprised 10228 patients treated for GGG1 PC diagnosed via transrectal ultrasound (TRUS)-guided systematic biopsy (SBx; n = 9248) or combined biopsy (CBx; SBx + TRUS/magnetic resonance image [MRI] fusion biopsy; n = 980) from a cohort study at a university hospital in Hamburg, Germany. We used logistic, Fine and Grays, and Cox multivariable regression methods to calculate the adjusted odds ratio (aOR) of adverse pathology and adjusted hazard ratios (aHRs) for early prostate-specific antigen (PSA) failure (≤18 mo), PCSM, and ACM in relation to each clinical factor. KEY FINDINGS AND LIMITATIONS: Irrespective of biopsy approach, percent positive biopsies (PPB) >50% and PSA >20 ng/ml were significantly associated with higher risk of adverse pathology (SBx: aOR 1.71 and 3.49; CBx: aOR 1.81 and 2.82, respectively) and early PSA failure (SBx: aHR 1.54 and 4.37; CBx: aHR 2.88 and 7.81, respectively). PPB >50% and PSA >20 ng/ml were also associated with higher risk of PCSM (aHRs 2.56 and 3.71) and ACM (aHRs 1.47 and 2.00) in the SBx group (all p ≤ 0.04). The study is limited by the single-institution cohort design. CONCLUSION AND CLINICAL IMPLICATION: Maintaining the "cancer" classification for patients with GGG1 and either PPB >50% or PSA>20 ng/ml and considering rebiopsy to identify unsampled high-grade disease may minimize the risk of mortality for this subgroup. PATIENT SUMMARY: For patients undergoing non-targeted prostate biopsy, approximately 1 in 12 with a biopsy result of grade group 1 prostate cancer may have more aggressive cancer than the result suggests. A very high PSA (prostate-specific antigen) level (>20 ng/ml) or the presence of grade group 1 cancer in more than 50% of the biopsy samples can identify patients at risk.

14.
Biomed Environ Sci ; 37(5): 494-502, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38843922

RESUMO

Objective: To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury (DILI) caused by different drugs and their correlation with clinical indicators. Method: The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests (RUCAM) scoring criteria and clinically diagnosed with DILI. Based on Chinese herbal medicine, cardiovascular drugs, non-steroidal anti-inflammatory drugs (NSAIDs), anti-infective drugs, and other drugs, patients were divided into five groups. Cytokines were measured by Luminex technology. Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results: 73 patients were enrolled. Age among five groups was statistically different ( P = 0.032). Alanine aminotransferase (ALT) ( P = 0.033) and aspartate aminotransferase (AST) ( P = 0.007) in NSAIDs group were higher than those in chinese herbal medicine group. Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with Chinese herbal medicine (IL-6: P < 0.001; TNF-α: P < 0.001) and cardiovascular medicine (IL-6: P = 0.020; TNF-α: P = 0.001) were lower than those in NSAIDs group. There was a positive correlation between ALT ( r = 0.697, P = 0.025), AST ( r = 0.721, P = 0.019), and IL-6 in NSAIDs group. Conclusion: Older age may be more prone to DILI. Patients with NSAIDs have more severe liver damage in early stages of DILI, TNF-α and IL-6 may partake the inflammatory process of DILI.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Citocinas , Humanos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Masculino , Feminino , Pessoa de Meia-Idade , Citocinas/sangue , Citocinas/metabolismo , Adulto , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Medicamentos de Ervas Chinesas/efeitos adversos , Alanina Transaminase/sangue
15.
BMC Complement Med Ther ; 24(1): 240, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902771

RESUMO

BACKGROUND: Acupuncture is a method for treating tic disorder. However, there is a lack of sufficient clinical objective basis in regards of its treatment efficacy. Indeed, there are structural abnormalities present in energy metabolism and infrared thermography in children with tic disorder. Therefore, this study proposes a clinical trial scheme to explore the possible mechanism of acupuncture in treating tic disorder. METHODS: This randomized controlled trial will recruit a total of 90 children, in which they will be divided into non-intervention group and intervention group. The non-intervention group consists of 30 healthy children while the intervention group consists of 60 children with tic disorder. The intervention group will be randomly allocated into either the treatment group or the control group, with 30 children randomly assigned in each group. Children either received acupuncture treatment and behavioral therapy (treatment group) or sham acupuncture treatment and behavioral therapy (control group), 3 treatment sessions per week for a period of 12 weeks, with a total of 36 treatment sessions. Outcome measures include YGTSS, urinary and fecal metabolomics, infrared thermography of body surface including governor vessel. For the intervention group, these outcome measures will be collected at the baseline and 90th day prior to intervention. Whereas for the non-intervention group, outcome measures (excluding YGTSS) will be collected at the baseline. DISCUSSION: The main outcome will be to observe the changes of the severity of tic condition, the secondary outcome will be to observe the changes of structural characteristic of infrared thermography of body surface/acupoints along the governor vessel and to evaluate the changes of urinary and fecal metabolomics at the end of the treatment, so as to analyze the relationship between them and to provide further knowledge in understanding the possible mechanism of acupuncture in improving the clinical symptoms via regulating and restoring the body metabolomics network, which in future it can develop as a set of clinical guideline (diagnosis, treatment, assessment, prognosis) in treating tic disorder. ChiCTR2300075188(Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 29 August 2023).


Assuntos
Terapia por Acupuntura , Metabolômica , Termografia , Transtornos de Tique , Humanos , Termografia/métodos , Terapia por Acupuntura/métodos , Criança , Transtornos de Tique/terapia , Feminino , Masculino , Pré-Escolar , Adolescente , Raios Infravermelhos , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
World J Clin Cases ; 12(17): 3243-3252, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38898852

RESUMO

BACKGROUND: This case series investigated the clinical manifestations, diagnoses, and treatment of cerebral abscesses caused by Streptococcus anginosus. We retrospectively analyzed the clinical characteristics and outcomes of three cases of cerebral abscesses caused by Streptococcus anginosus and conducted a comprehensive review of relevant literature. CASE SUMMARY: Case 1 presented with a history of left otitis media and exhibited high fever, confusion, and vomiting as primary symptoms. Postoperative pus culture indicated a brain abscess caused by Streptococcus constellatus infection. Case 2 experienced dizziness for two days as the primary symptom. Postoperative pus culture suggested an intermediate streptococcal brain abscess. Case 3: Enhanced head magnetic resonance imaging (MRI) and diffusion-weighted imaging revealed occupancy of the left temporal lobe, initially suspected to be a metastatic tumor. However, a postoperative pus culture confirmed the presence of a brain abscess caused by Streptococcus anginosus infection. The three cases presented in this case series were all patients with community-acquired brain abscesses resulting from angina caused by Streptococcus group infection. All three patients demonstrated sensitivity to penicillin, ceftriaxone, vancomycin, linezolid, chloramphenicol, and levofloxacin. Successful treatment was achieved through stereotaxic puncture, drainage, and ceftriaxone administration with a six -week course of antibiotics. CONCLUSION: Preoperative enhanced head MRI plays a critical role in distinguishing brain tumors from abscesses. Selecting the correct early diagnostic methods for brain abscesses and providing timely intervention are very important. This case series was in accordance with the CARE guidelines.

17.
Anal Chem ; 96(25): 10356-10364, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38863415

RESUMO

Capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D) has proven to be an efficient technique for the separation and detection of charged inorganic, organic, and biochemical analytes. It offers several advantages, including cost-effectiveness, nanoliter injection volume, short analysis time, good separation efficiency, suitability for miniaturization, and portability. However, the routine determination of common inorganic cations (NH4+, K+, Na+, Ca2+, Mg2+, and Li+) and inorganic anions (F-, Cl-, Br-, NO2-, NO3-, PO43-, and SO42-) in water quality monitoring typically exhibits limits of detection of about 0.3-1 µM without preconcentration. This sensitivity often proves insufficient for the applications of CE-C4D in trace analysis situations. Here, we explore methods to push the detection limits of CE-C4D through a comprehensive consideration of signal and noise sources. In particular, we (i) studied the model of C4D and its guiding roles in C4D and CE-C4D, (ii) optimized the bandwidth and noise performance of the current-to-voltage (I-V) converter, and (iii) reduced the noise level due to the strong background signal of the background electrolyte by adaptive differential detection. We characterized the system with Li+; the 3-fold signal-to-noise (S/N) detection limit for Li+ was determined at 20 nM, with a linear range spanning from 60 nM to 1.6 mM. Moreover, the optimized CE-C4D method was applied to the analysis of common mixed inorganic cations (K+, Na+, Ca2+, Mg2+, and Li+), anions (F-, Cl-, Br-, NO2-, NO3-, PO43-, and SO42-), toxic halides (BrO3-) and heavy metal ions (Pb2+, Cd2+, Cr3+, Co2+, Ni2+, Zn2+, and Cu2+) at trace concentrations of 200 nM. All electropherograms showed good S/N ratios, thus proving its applicability and accuracy. Our results have shown that the developed CE-C4D method is feasible for trace ion analysis in water quality control.

18.
Ann Transl Med ; 12(3): 47, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38911563

RESUMO

Background: Chronic kidney disease (CKD) is significantly influenced by mitochondrial dysfunction (MD). Previous research suggests that methylmalonic acid (MMA) is involved in MD. Consequently, we aimed to investigate associations between blood MMA level and the prevalence of CKD as well as mortality in patients with CKD. Methods: The study included 23,587 individuals from National Health and Nutrition Examination Survey (NHANES). The NHANES datasets from 1999-2004 and 2011-2014 were utilized as separate primary and validation subsets. There were 3,554 patients with CKD. The association of blood MMA level with the prevalence of CKD was investigated using weighted logistic regression. Meanwhile, we employed weighted Cox regression models to evaluate the association between blood MMA level and all-cause mortality in patients with CKD. Results: Blood MMA levels had a significant positive association with urinary albumin-to-creatinine ratio (ß=45.29, P=0.01) and negative association with estimated glomerular filtration rate (ß=-15.27, P<0.001) in CKD patients. Blood MMA level exhibited a significant increase in participants with CKD compared with those without CKD (7.60±0.86 vs. 7.03±0.62, P<0.001). The level of blood MMA was significantly associated with the prevalence of CKD [odds ratio (OR): 1.32, 95% confidence interval (CI): 1.05-1.64, P=0.01]. In addition, blood MMA level was significantly associated with all-cause mortality in CKD participants [hazard ratio (HR): 1.26, 95% CI: 1.11-1.43, P<0.001] after adjusting for other potential predictors. Conclusions: Increased blood MMA levels were associated with more severe kidney impairment and increased risk of both the prevalence of CKD and mortality in participants with CKD.

19.
J Nanobiotechnology ; 22(1): 361, 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38910236

RESUMO

Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.


Assuntos
Autofagia , Temperatura Baixa , Exossomos , Camundongos Endogâmicos C57BL , MicroRNAs , Osteogênese , Animais , Autofagia/efeitos dos fármacos , Camundongos , Exossomos/metabolismo , MicroRNAs/metabolismo , MicroRNAs/genética , Osteogênese/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Osteoporose/patologia , Diferenciação Celular/efeitos dos fármacos , Osso e Ossos/metabolismo , Feminino , Densidade Óssea , Sirolimo/farmacologia
20.
Bioorg Med Chem ; 110: 117793, 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38917622

RESUMO

The pathogenic role of anti-phospholipase A2 receptor (PLA2R) antibodies in primary membranous nephropathy (MN) has been well-established. This study aimed to identify potential small-molecule inhibitors against the PLA2R-antibody interaction, offering potential therapeutic benefits. A comprehensive screening of over 4000 small-molecule compounds was conducted by ELISA to assess their inhibitory effects on the binding between the immobilized full-length extracellular PLA2R and its antibodies. The affinity of anti-PLA2R IgG from MN patients and the inhibitory efficacy of each compound were evaluated via surface plasmon resonance (SPR). Human podocyte injuries were analyzed using CCK-8 assay, wound healing assay, western blot analysis, and immunofluorescence, after exposure to MN plasma +/- blocking compound. Fifteen compounds were identified as potential inhibitors, demonstrating inhibition rates >20 % for the PLA2R-antibody interaction. Anti-PLA2R IgG exhibited a consistent affinity among patients (KD = 10-8 M). Macrocarpal B emerged as the most potent inhibitor, reducing the antigen-antibody interaction by nearly 30 % in a dose-dependent manner, comparable to the performance of the 31-mer peptide from the CysR domain. Macrocarpal B bound to the immobilized PLA2R with an affinity of 1.47 × 10-6 M, while showing no binding to anti-PLA2R IgG. Human podocytes exposed to MN plasma showed decreased podocin expression, impaired migration function, and reduced cell viability. Macrocarpal B inhibited the binding of anti-PLA2R IgG to podocytes and reduced the cellular injuries.

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