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1.
Nano Lett ; 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39373272

RESUMEN

Supramolecular polymers hold promise in thermal management applications due to their multistability, high responsiveness, and cost-effectiveness. In this work, we successfully regulate phonon transport at the molecular level in supramolecular polymers by adjusting the strength of intermolecular hydrogen bonding. We synthesized three supramolecular polymer fibers with thermal conductivity differences of up to 289% based on melamine (M) and three simple positional isomers of hydroxybenzoic acid. Differential Scanning Calorimetry (DSC) measurement revealed discrepancies in thermal stability of the polymers, where structures with higher stability exhibited enhanced thermal conductivity. Fourier Transform Infrared Spectroscopy (FTIR) measurement and Density Functional Theory (DFT) calculations indicate that these differences arise from variations in hydrogen-bonding strengths at different bonding sites. Higher hydrogen-bonding strength leads to more stable thermal pathways, reduces phonon scattering, and increases thermal conductivity. Our findings provide valuable insights into controlling the thermal conductivity of polymer fibers, paving the way for applications in phonon-based thermal devices.

2.
J Neuroeng Rehabil ; 21(1): 176, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39354619

RESUMEN

BACKGROUND: Extracorporeal shockwave therapy (ESWT) has been proven beneficial for post-stroke spasticity (PSS) of ankle plantar flexor muscles. This study aims to investigate the dose-response effectiveness of focused-ESWT and the duration of its effect on the treatment of ankle PSS in stroke patients. METHODS: In this double-blinded randomized controlled trial, stroke patients diagnosed with PSS in the ankle plantar flexor muscles were randomly assigned to two groups. The experimental group received double-dose ESWT (4000 pulses per session) targeting spastic calf muscles, while the control group received half the dose (2000 pulses per session). Both groups underwent four sessions over two weeks. The outcomes, including modified Ashworth Scale (MAS), modified Tardieu Scale (MTS), passive range of motion (PROM) of the ankle, Timed Up and Go (TUG) Test, Barthel index and strain elastography were evaluated at baseline, 1st, 4th, 12th, and 24th week after ESWT. RESULTS: Within-group analysis revealed significant improvements in MAS, PROM, TUG Test, and Barthel index for the double-dose ESWT group and improvements in Barthel index for the control group. Between-group analysis revealed greater improvements in TUG Test, Barthel Index and strain elastography for the double-dose ESWT group. Generalized estimating equations analysis indicated that the double-dose ESWT group achieved superior outcomes in the TUG Test, Barthel Index, and strain elastography across various time points and groups. CONCLUSIONS: Double-dose ESWT showed better functional improvement and elastography compared to the control group. ESWT demonstrated dose-response effectiveness for PSS of ankle-equinus. TRIAL REGISTRATION: NCT05878223.


Asunto(s)
Tratamiento con Ondas de Choque Extracorpóreas , Espasticidad Muscular , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Espasticidad Muscular/etiología , Espasticidad Muscular/rehabilitación , Espasticidad Muscular/terapia , Masculino , Tratamiento con Ondas de Choque Extracorpóreas/métodos , Femenino , Persona de Mediana Edad , Método Doble Ciego , Accidente Cerebrovascular/complicaciones , Rehabilitación de Accidente Cerebrovascular/métodos , Tobillo , Resultado del Tratamiento , Adulto , Anciano , Rango del Movimiento Articular , Articulación del Tobillo
3.
Clin Kidney J ; 17(9): sfae264, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39286239

RESUMEN

Background: The remission rate of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients who received standard induction therapy is far from satisfactory. Improving the remission rate of MPO-AAV patients is essential. Hydroxychloroquine (HCQ), one of the classic antimalarial drugs, has been widely used in various autoimmune rheumatic diseases. This retrospective observational cohort study is aimed to evaluate the efficacy and safety of HCQ during induction treatment for MPO-AAV. Methods: The medical records of patients diagnosed with MPO-AAV at Xiangya Hospital, Central South University from January 2021 to September 2023 were collected. They were assigned to the HCQ group or control group according to whether they used HCQ. The patients included were screened by propensity score matching. To evaluate whether MPO-AAV patients benefited from HCQ, we compared the prognosis of the two groups. The adverse effects of HCQ during follow-up were recorded. Results: The composition ratio of complete remission, response and treatment resistance between HCQ group and control group were different statistically (P = .021). There was no significant difference between the two groups in 1-year renal survival (P = .789). The HCQ group had better 1-year patient survival than the control group (P = .049). No serious adverse effects were documented in the HCQ group. Conclusions: HCQ together with standard induction treatment may improve the remission rate of MPO-AAV patients, and HCQ had good safety in our study.

4.
Acta Otolaryngol ; : 1-10, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225593

RESUMEN

BACKGROUND: Scopolamine has been demonstrated to relieve motion sickness. However, repeated significance testing may increase false-positive results. OBJECTIVES: Review the efficacy and safety of scopolamine in the prevention of motion sickness by performing a meta-analysis with Trial Sequential Analysis (TSA). MATERIAL AND METHODS: Randomized controlled trials (RCTs) compared scopolamine with other medications or placebo were included. Primary outcomes were nausea reported and head movement time. RESULTS: Twenty studies with 753 participants were included. Scopolamine had a greater reported reduction in nausea than placebo (relative risk [RR] 0.35; 95% confidence interval [CI] 0.24 to 0.52; p<0.00001; I2 = 45%), while TSA showed the included sample size exceeded the required information size (RIS). There is no difference in head movement time between scopolamine and placebo (mean difference [MD] 2.02; 95% CI -1.2 to 5.25; p = 0.6; I2 = 0%), while the included sample size did not reach RIS. CONCLUSION: Scopolamine is effective for motion sickness nausea compared to placebo. The TSA recommends conducting more head movement trials to validate the objective efficacy of scopolamine. SIGNIFICANCE: Clarifying the efficacy of scopolamine for motion sickness, the TSA highlights the need for more prospective studies using head movement as an outcome.

5.
Cardiovasc Diabetol ; 23(1): 335, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39261922

RESUMEN

BACKGROUND: Observational studies have revealed associations between maternal lipid metabolites and gestational diabetes mellitus (GDM). However, whether these associations are causal remain uncertain. OBJECTIVE: To evaluate the causal relationship between lipid metabolites and GDM. METHODS: A two-sample Mendelian randomization (MR) analysis was performed based on summary statistics. Sensitivity analyses, validation analyses and reverse MR analyses were conducted to assess the robustness of the MR results. Additionally, a phenome-wide MR (Phe-MR) analysis was performed to evaluate potential side effects of the targeted lipid metabolites. RESULTS: A total of 295 lipid metabolites were included in this study, 29 of them had three or more instrumental variables (IVs) suitable for sensitivity analyses. The ratio of triglycerides to phosphoglycerides (TG_by_PG) was identified as a potential causal biomarker for GDM (inverse variance weighted (IVW) estimate: odds ratio (OR) = 2.147, 95% confidential interval (95% CI) 1.415-3.257, P = 3.26e-4), which was confirmed by validation and reverse MR results. Two other lipid metabolites, palmitoyl sphingomyelin (d18:1/16:0) (PSM(d18:1/16:0)) (IVW estimate: OR = 0.747, 95% CI 0.583-0.956, P = 0.021) and triglycerides in very small very low-density lipoprotein (XS_VLDL_TG) (IVW estimate: OR = 2.948, 95% CI 1.197-5.215, P = 0.015), were identified as suggestive potential biomarkers for GDM using a conventional cut-off P-value of 0.05. Phe-MR results indicated that lowering TG_by_PG had detrimental effects on two diseases but advantageous effects on the other 13 diseases. CONCLUSION: Genetically predicted elevated TG_by_PG are causally associated with an increased risk of GDM. Side-effect profiles indicate that TG_by_PG might be a target for GDM prevention, though caution is advised due to potential adverse effects on other conditions.


Asunto(s)
Biomarcadores , Diabetes Gestacional , Lipidómica , Lípidos , Análisis de la Aleatorización Mendeliana , Humanos , Diabetes Gestacional/sangre , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/genética , Femenino , Embarazo , Factores de Riesgo , Lípidos/sangre , Medición de Riesgo , Biomarcadores/sangre , Fenotipo , Predisposición Genética a la Enfermedad , Reproducibilidad de los Resultados , Fenómica
6.
Eur Geriatr Med ; 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39317881

RESUMEN

PURPOSE: To identify the predictive variables for post-stroke dysphagia (PSD) among anterior circulation large vessel occlusion (LVO) stroke patients who underwent endovascular thrombectomy (EVT). METHODS: This retrospective cohort study enrolled hospitalized patients with anterior LVO stroke who underwent EVT between January 1, 2018 and October 31, 2022. PSD was defined as the unsuccessful removal of the nasogastric (NG) tube. Factors, such as premorbid characteristics, laboratory results, EVT, rehabilitation-related parameters, and neuro-imaging, were analyzed for correlations to PSD at 4 and 12 weeks. RESULTS: The study enrolled 136 patients, with a mean age of 72.9 ± 13.0 years, and 59 patients (43.4%) were male. At 4 weeks, 47.1% of the patients needed an NG tube, and at 12 weeks, 16.2% still required an NG tube. We found that lower albumin, lower body mass index (BMI), higher initial and 24-h post-EVT National Institute of Health Stroke Scale (NIHSS) scores, stroke-associated pneumonia, poor initial sitting balance and ability to sit up, insula or frontal operculum lesions, and bilateral hemisphere involvement were all associated with PSD at both 4 and 12 weeks in the univariate logistic regression. Multivariate analysis revealed that significant predictors of unsuccessful NG tube removal at 4 weeks included lower BMI (adjusted OR [aOR] 0.73, p = 0.005), hemorrhagic transformation (aOR 4.01, p = 0.0335), higher NIHSS scores at 24 h post-EVT (aOR 1.13, p = 0.0288), poor initial sitting ability (aOR 0.52, p = 0.0231), insular cortex ischemia (aOR 7.26, p = 0.0056), and bilateral hemisphere involvement (aOR 41.19, p < 0.0001). At 12 weeks, lower BMI (aOR 0.78, p = 0.0098), poor initial sitting balance (aOR 0.57, p = 0.0287), insular cortex lesions (aOR 4.83, p = 0.0092), and bilateral hemisphere involvement (aOR 4.07, p = 0.0139) remained significant predictors. CONCLUSIONS: In patients with anterior LVO following EVT, PSD was associated with lower BMI, higher NIHSS scores, poor initial sitting balance and sitting ability, insular lesions, and bilateral hemisphere involvement.

7.
Org Biomol Chem ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39318223

RESUMEN

A convenient method for synthesizing ß-trifluoromethyl vinyl ethers and diethers through the base-mediated C-O coupling of (E)-1,2-dichloro-3,3,3-trifluoroprop-1-ene and phenols has been developed. Remarkably, the present process shows perfect regioselective and stereoselective yield of the Z/E isomers for ß-trifluoromethyl vinyl ethers with high efficiency. Additionally, ß-trifluoromethyl vinyl diethers with identical/diverse phenoxy groups were also obtained and the regulation of the product configuration was achieved. These reactions feature transition-metal-free conditions, wide substrate scope, and atom economy.

8.
Ann Med ; 56(1): 2405073, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39301858

RESUMEN

BACKGROUND: Thrombocytopenia is commonly observed in patients with sepsis and is an independent risk factor for poor prognosis. However, the changes of platelet count caused by different pathogens can vary significantly. Our study aims to evaluate the quantitative changes in platelet count in response to various pathogens. MATERIAL AND METHODS: We retrospectively analysed data of 3044 patients with sepsis from Medical Information Mart for Intensive Care (MIMIC, 2008-2019) database and prospectively collected data of 364 patients with sepsis from our local cohort of the Shandong Bloodstream Infection and Sepsis Collaboration Study (SBISC, 2020-2022). Propensity score matching (PSM) was employed to control for baseline differences in variables, except for the causative pathogen. RESULTS: Multivariate logistic analyses of both original and PSM populations identified Candida, Escherichia, Klebsiella, and Serratia species posing a higher risk for thrombocytopenia compared to others. Restricted cubic spline (RCS) curves showed L- or U-shaped associations between platelet count and 28-mortality with various cut-off values among different pathogens: ranging from 96 × 109/L in Candida species - 190 × 109/L in Klebsiella species. CONCLUSION: Our present findings indicate a pathogen-specific effect on platelet count, highlighting the importance of monitoring thrombocytopenia in patients infected with above microorganisms. Clinicians need to consider pathogen-specific thresholds when intervene on platelet count.


This study validated the differential incidence of thrombocytopenia among various pathogens within two distinct populations.Candida, Escherichia, Klebsiella, and Serratia species were identified as having a notably higher risk of causing thrombocytopenia compared to other pathogens.We observed L- or U-shaped relationships between platelet counts and 28-day mortality in Candida species, Enterococcus species, Escherichia species, Enterobacter species, Staphylococcus species, and Klebsiella species with platelet count cutoff values of 96 × 109/L, 100 × 109/L, 100 × 109/L, 146 × 109/L, 152 × 109/L, and 190 × 109/L, respectively.


Asunto(s)
Sepsis , Trombocitopenia , Humanos , Masculino , Femenino , Sepsis/sangre , Sepsis/microbiología , Estudios Retrospectivos , Recuento de Plaquetas , Persona de Mediana Edad , Trombocitopenia/sangre , Trombocitopenia/microbiología , Anciano , Estudios Prospectivos , Klebsiella/aislamiento & purificación , Factores de Riesgo , Candida/aislamiento & purificación , Serratia/aislamiento & purificación , Puntaje de Propensión
9.
Cell Discov ; 10(1): 92, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39223112

RESUMEN

Human ABC transporters ABCD1-3 are all localized on the peroxisomal membrane and participate in the ß-oxidation of fatty acyl-CoAs, but they differ from each other in substrate specificity. The transport of branched-chain fatty acids from cytosol to peroxisome is specifically driven by ABCD3, dysfunction of which causes severe liver diseases such as hepatosplenomegaly. Here we report two cryogenic electron microscopy (cryo-EM) structures of ABCD3 bound to phytanoyl-CoA and ATP at resolutions of 2.9 Å and 3.2 Å, respectively. A pair of phytanoyl-CoA molecules were observed in ABCD3, each binding to one transmembrane domain (TMD), which is distinct from our previously reported structure of ABCD1, where each fatty acyl-CoA molecule strongly crosslinks two TMDs. Upon ATP binding, ABCD3 exhibits a conformation that is open towards the peroxisomal matrix, leaving two extra densities corresponding to two CoA molecules deeply embedded in the translocation cavity. Structural analysis combined with substrate-stimulated ATPase activity assays indicated that the present structures might represent two states of ABCD3 in the transport cycle. These findings advance our understanding of fatty acid oxidation and the molecular pathology of related diseases.

10.
Ying Yong Sheng Tai Xue Bao ; 35(6): 1573-1582, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-39235015

RESUMEN

Low temperature (LT) in spring usually occurs at the booting of winter wheat, resulting in reduction of wheat yield. In this study, we used the LT-sensitive wheat cultivar 'Wanmai 52' and the LT-insensitive wheat cultivar 'Yannong 19' as experimental materials to conduct LT treatment (-2 ℃ and 0 ℃) at booting stage. After the LT treatment, we sprayed 6-benzylaminoadenine (6-BA) solutions with concentrations of 10, 20, and 30 mg·L-1 respectively, with equal mass distilled water as control to investigate the effects of spraying 6-BA on the physiological characteristics, yield and quality of wheat flag leaves after LT stress at booting stage. The results showed that compared with the control, young ear of wheat treated with exogenous spraying 6-BA was fuller, the floret morphology was improved, and the number of vascular bundles under the spike was increased. 6-BA application promoted the accumulation of soluble sugar, soluble protein, and proline in flag leaves. The activities of peroxidase and superoxide dismutase were increased, and the content of malondialdehyde was decreased. Exogenous 6-BA application decreased the number of degenerated spikes of wheat, increased the number of grains per spike and 1000-grain weight, as well as the contents of grain protein, wet gluten, and sedimentation value. In summary, exogenous 6-BA application could effectively alleviate the effects of LT stress on flag leaf and yield of wheat. Under the conditions of this experiment, the mitigation effect of spraying 6-BA solution on Yannong 19 was higher than that of Wanmai 52, and the mitigation effect of spraying 20 mg·L-1 6-BA solution on low temperature stress was the best.


Asunto(s)
Frío , Hojas de la Planta , Purinas , Estrés Fisiológico , Triticum , Triticum/crecimiento & desarrollo , Triticum/metabolismo , Triticum/efectos de los fármacos , Triticum/fisiología , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Purinas/farmacología , Biomasa , Reguladores del Crecimiento de las Plantas/farmacología , Control de Calidad , Compuestos de Bencilo
11.
Clin Nutr ; 43(10): 2327-2335, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39232261

RESUMEN

BACKGROUND & AIMS: Malnutrition is prevalent among hospitalised patients, and increases the morbidity, mortality, and medical costs; yet nutritional assessments on admission are not routine. This study assessed the clinical and economic benefits of using an artificial intelligence (AI)-based rapid nutritional diagnostic system for routine nutritional screening of hospitalised patients. METHODS: A nationwide multicentre randomised controlled trial was conducted at 11 centres in 10 provinces. Hospitalised patients were randomised to either receive an assessment using an AI-based rapid nutritional diagnostic system as part of routine care (experimental group), or not (control group). The overall medical resource costs were calculated for each participant and a decision-tree was generated based on an intention-to-treat analysis to analyse the cost-effectiveness of various treatment modalities. Subgroup analyses were performed according to clinical characteristics and a probabilistic sensitivity analysis was performed to evaluate the influence of parameter variations on the incremental cost-effectiveness ratio (ICER). RESULTS: In total, 5763 patients participated in the study, 2830 in the experimental arm and 2933 in the control arm. The experimental arm had a significantly higher cure rate than the control arm (23.24% versus 20.18%; p = 0.005). The experimental arm incurred an incremental cost of 276.52 CNY, leading to an additional 3.06 cures, yielding an ICER of 90.37 CNY. Sensitivity analysis revealed that the decision-tree model was relatively stable. CONCLUSION: The integration of the AI-based rapid nutritional diagnostic system into routine inpatient care substantially enhanced the cure rate among hospitalised patients and was cost-effective. REGISTRATION: NCT04776070 (https://clinicaltrials.gov/study/NCT04776070).


Asunto(s)
Inteligencia Artificial , Análisis Costo-Beneficio , Hospitalización , Desnutrición , Evaluación Nutricional , Humanos , Masculino , Femenino , Inteligencia Artificial/economía , Anciano , Persona de Mediana Edad , Desnutrición/diagnóstico , Desnutrición/economía , Hospitalización/economía , Estado Nutricional , Anciano de 80 o más Años , Adulto
12.
Ecotoxicol Environ Saf ; 284: 116999, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39244879

RESUMEN

Chloro-haloacetonitrile (Cl-HAN), belongs to a group of nitrogenous disinfection by-products (N-DBPs) found in surface water, and are known to pose a major risk to the safety of human drinking water. However, the exact biological toxicity mechanism and the extent of the stress response caused by Cl-HAN remain unclear, resulting in a lack of effective measures to control its presence. Thus, the quantitative toxicological genomics and bioinformatics methods were applied to explore the effects of three chloro-haloacetonitriles (Cl-HANs) on the transcription of fusion genes under varying concentrations of stress in E. coli over 2-hour period. The initial stress response and their toxic mechanism were analyzed. The study also identified the molecular toxicity endpoint, and the core genes that are responsible for the specific toxicity of different Cl-HANs. Cl-HANs exhibited concentration-dependent characteristics of toxic effects, and caused changes in gene expression related oxidative and membrane stress. The stress response results showed that dichloroacetonitrile (dCAN) still caused significant DNA damage under the lowest concentration stress. Chloroacetonitrile (CAN) and trichloroacetonitrile (tCAN) exhibited lower genetic toxicity levels at 513 µg/L and 10.7 µg/L, respectively. The toxic effects of tCAN were widespread. And there was a good correlation between the molecular endpoint (EC-TELI1.5) and the phenotypic endpoint (LD50) with rp=-0.8634 (P=0.0593). In all concentrations of stress in CAN, dCAN, and tCAN, the number of overexpressed genes shared was 15, 2, and 14, respectively. Furthermore, bioinformatics analysis demonstrated that Cl-HANs affected genes associated with general stress pathways, such as cell biochemistry and physical homeostasis, resulting in changes in biological processes. And for CAN-induced DNA damage, polA played a dominant role, while katG, oxyR, and ahpC were the core genes involved in oxidative stress induced by dCAN and tCAN, respectively. These findings provide valuable data for the toxic effect of Cl-HANs.


Asunto(s)
Acetonitrilos , Daño del ADN , Escherichia coli , Contaminantes Químicos del Agua , Acetonitrilos/toxicidad , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Contaminantes Químicos del Agua/toxicidad , Estrés Oxidativo/efectos de los fármacos , Estrés Fisiológico/efectos de los fármacos , Desinfectantes/toxicidad
13.
Free Radic Biol Med ; 224: 630-643, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39299527

RESUMEN

Ectopic lipid accumulation induced lipotoxicity plays a crucial role in exacerbating the development of metabolic dysfunction-associated steatotic liver disease (MASLD), which affects over 30% of the worldwide population and 85% of the obese population. The growing demand for effective therapeutic agents highlights the need for high-efficacy lipotoxicity ameliorators and relevant therapeutic targets in the fight against MASLD. This study aimed to discover natural anti-lipotoxic and anti-MASLD candidates and elucidate the underlying mechanism and therapeutic targets. Utilizing palmitic acid (PA)-induced HepG-2 and primary mouse hepatocyte models, we identified linoleic acid (HN-002), a ligand of fatty acid binding protein 4 (FABP4), from the marine fungus Eutypella sp. F0219. HN-002 dose-dependently prevented lipid overload-induced hepatocyte damage and lipid accumulation, inhibited fatty acid esterification, and ameliorated oxidative stress. These beneficial effects were associated with improvements in mitochondrial adaptive oxidation. HN-002 treatment enhanced lipid transport into mitochondria and oxidation, inhibited mitochondrial depolarization, and reduced mitochondrial ROS (mtROS) level in PA-treated hepatocytes. Mechanistically, HN-002 treatment disrupted the interaction between KEAP1 and NRF2, leading to NRF2 deubiquitylation and nuclear translocation, which activated beneficial metabolic regulation. In vivo, HN-002 treatment (20 mg/kg/per 2 days, i. p.) for 25 days effectively reversed hepatic steatosis and liver injury in the fast/refeeding plus high-fat/high-cholesterol diet induced MASLD mice. These therapeutic effects were associated with enhanced mitochondrial adaptive oxidation and activation of NRF2 signaling in the liver. These data suggest that HN-002 would be an interesting candidate for MASLD by improving mitochondrial oxidation via the FABP4/KEAP1/NRF2 axis. The discovery offers new insights into developing novel anti- MASLD agents derived from marine sources.

14.
J Transl Med ; 22(1): 870, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39334140

RESUMEN

BACKGROUND: Diabetic retinopathy (DR), the principal cause of acquired blindness among the working-age population, is the most frequent microvascular complication of diabetes. Although metabolic disorders are hypothesized to play a role in its pathogenesis, the underlying mechanism remains largely elusive. METHODS: To elucidate the mechanism, we initially compared metabolite profiles of vitreous fluid between 23 patients with DR and 12 non-diabetic controls using liquid chromatography/tandem mass spectrometry, identifying the distinct metabolite indoxyl sulfate (IS). Subsequently, streptozotocin (STZ)-induced diabetic and IS-injected rat models were established to examine the effects of IS on retinal microvasculature. RNA sequencing was conducted to identify potential regulatory mechanisms in IS-treated human retinal endothelial cells (HREC). Finally, target gene knockdown in HREC and treatment of IS-injected rats with inhibitors (targeting IS production or downstream regulators) were employed to elucidate the detailed mechanisms and identify therapeutic targets for DR. RESULTS: Metabolomics identified 172 significantly altered metabolites in the vitreous humor of diabetics, including the dysregulated tryptophan metabolite indoxyl sulfate (IS). IS was observed to breach the blood-retinal barrier and accumulate in the intraocular fluid of diabetic rats. Both in vivo and in vitro experiments indicated that elevated levels of IS induced endothelial apoptosis and disrupted cell junctions. RNA sequencing pinpointed prostaglandin E2 (PGE2) synthetase-cyclooxygenase 2 (COX-2) as a potential target of IS. Validation experiments demonstrated that IS enhanced COX-2 expression, which subsequently increased PGE2 secretion by promoting transcription factor EGR1 binding to COX-2 DNA following entry into cells via organic anion transporting polypeptides (OATP2B1). Furthermore, inhibition of COX-2 in vivo or silencing EGR1/OATP2B1 in HREC mitigated IS-induced microcapillary damage and the activation of COX-2/PGE2. CONCLUSION: Our study demonstrated that indoxyl sulfate (IS), a uremic toxin originating from the gut microbiota product indole, increased significantly and contributed to retinal microvascular damage in diabetic retinopathy (DR). Mechanistically, IS impaired retinal microvascular integrity by inducing the expression of COX-2 and the production of PGE2. Consequently, targeting the gut microbiota or the PGE2 pathway may offer effective therapeutic strategies for the treatment of DR.


Asunto(s)
Ciclooxigenasa 2 , Diabetes Mellitus Experimental , Retinopatía Diabética , Dinoprostona , Indicán , Microvasos , Retinopatía Diabética/patología , Retinopatía Diabética/metabolismo , Animales , Humanos , Ciclooxigenasa 2/metabolismo , Dinoprostona/metabolismo , Masculino , Microvasos/patología , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Ratas Sprague-Dawley , Células Endoteliales/metabolismo , Células Endoteliales/efectos de los fármacos , Vasos Retinianos/metabolismo , Vasos Retinianos/patología , Vasos Retinianos/efectos de los fármacos , Ratas , Persona de Mediana Edad , Retina/patología , Retina/metabolismo , Retina/efectos de los fármacos , Apoptosis/efectos de los fármacos
15.
Carbohydr Polym ; 346: 122616, 2024 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-39245526

RESUMEN

Traditional Fenton principles for degrading polysaccharides, including chondroitin sulfate (CS), are fraught with limitations, such as strict pH-dependence, higher temperature requirements, desulfurization, and environmentally perilous. In this study, an effective Fenton-like system comprising trimetallic-doped carbon nitride material (tri-CN) with hydrogen-bonded melamine-cyanuric acid (MCA) supramolecular aggregates as its basic skeleton was engineered to overcome the challenges of traditional methods. Detailed material characterizations revealed that, compared to monometallic-doped or bimetallic-doped counterparts, tri-CN offered a larger surface area, higher porosity, and increased metal loading, thereby enhancing reactant accessibility and polysaccharide degradation efficiency. The characterization and activity assessment of the degraded polysaccharide revealed structurally intact products without significant desulfurization, indicating the effectiveness of the designed approach. Moreover, the degraded chondroitin sulfate CS3 catalyzed by tri-CN, exhibited promising antioxidant activity and anti-CRISPR potential. The results elucidated that the high-valent iron species in the material served as primary active sites, catalyzing the cleavage of hydrogen peroxide to generate hydroxyl radicals that subsequently attacked CS chains, leading to their fragmentation. Hence, the designed material can be efficiently applied to polysaccharide degradation, but not limited to photocatalysis, electrocatalysis, sensor, energy storage materials, and wastewater treatment.

16.
Clin Nephrol ; 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39282890

RESUMEN

OBJECTIVE: To construct and apply a risk screening and intervention system for malnutrition in peritoneal dialysis patients based on the Omaha System. MATERIALS AND METHODS: A total of 75 peritoneal dialysis patients were randomly divided into control (38 cases) and intervention group (37 cases). The control group received routine operation training and health education, and the intervention group implemented a nutritional management plan based on the Omaha System. The modified quantitative subjective comprehensive nutritional scale (MQSGA) score, kidney disease dietary compliance attitude (RAAQ) and behavior (RABQ) score, body mass index (BMI), serum albumin (ALB), prealbumin (PA), and hemoglobin (Hb) were observed. RESULTS: Before intervention, there was no significant difference in these indicators between the two groups (p > 0.05). After 6 months, the MQSGA score in the intervention group was significantly lower than that in the control group (p < 0.05). RAAQ score and RABQ score in the intervention group were higher than those in the control group and (p < 0.05), and the nutritional indicators in the intervention group, such as BMI, ALB, PA, and Hb, were higher than those in the control group (p < 0.05). CONCLUSION: A nutritional management plan based on the Omaha System can help improve the nutrition condition of peritoneal dialysis patients, and improve the dietary compliance of chronic kidney disease patients.

17.
Curr Microbiol ; 81(11): 358, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39285060

RESUMEN

Antagonistic bacterial strains from Bacillus spp. have been widely studied and utilized in the biocontrol of phytopathogens and the promotion of plant growth, but their impacts on the rhizosphere microecology when applied to crop plants are unclear. Herein, the effects of applying the antagonistic bacterium Bacillus subtilis S1 as a biofertilizer on the rhizosphere microecology of cucumbers were investigated. In a pot experiment on cucumber seedlings inoculated with S1, 3124 bacterial operational taxonomic units (OTUs) were obtained from the rhizosphere soils using high-throughput sequencing of 16S rRNA gene amplicons, and the most abundant phylum was Proteobacteria that accounted for 49.48% in the bacterial community. S1 treatment significantly reduced the abundances of soil bacterial taxa during a period of approximately 30 days but did not affect bacterial diversity in the rhizosphere soils of cucumbers. The enzymatic activities of soil nitrite reductase (S-Nir) and dehydrogenase (S-DHA) were significantly increased after S1 fertilization. However, the activities of soil urease (S-UE), cellulase (S-CL), and sucrase (S-SC) were significantly reduced compared to the control group. Additionally, the ammonium- and nitrate-nitrogen contents of S1-treated soil samples were significantly lower than those of the control group. S1 fertilization reshaped the rhizosphere soil bacterial community of cucumber plants. The S-CL activity and nitrate-nitrogen content in rhizosphere soil affected by S1 inoculation play important roles in altering the abundance of rhizosphere soil microbiota.


Asunto(s)
Bacillus subtilis , Bacterias , Cucumis sativus , Nitrógeno , Rizosfera , Microbiología del Suelo , Cucumis sativus/microbiología , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Nitrógeno/metabolismo , Bacterias/clasificación , Bacterias/genética , Bacterias/metabolismo , Bacterias/aislamiento & purificación , ARN Ribosómico 16S/genética , Fertilizantes/análisis , Suelo/química , Microbiota , Filogenia
18.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(9): 899-906, 2024.
Artículo en Chino | MEDLINE | ID: mdl-39267503

RESUMEN

OBJECTIVES: To investigate how maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation are associated with the incidence of ventricular septal defects (VSD) in offspring. METHODS: A case-control study was conducted, recruiting 426 mothers of infants with VSD under one year old and 740 mothers of age-matched healthy infants. A questionnaire survey collected data on maternal exposures, and blood samples were analyzed for genetic polymorphisms. Multivariable logistic regression analysis and inverse probability of treatment weighting were used to analyze the associations between genetic loci and VSD. Crossover analysis and logistic regression were utilized to examine the additive and multiplicative interactions between the loci and folic acid intake. RESULTS: The CT and TT genotypes of the maternal MTR gene at rs6668344 increased the susceptibility of offspring to VSD (P<0.05). The GC and CC genotypes at rs3768139, AG and GG at rs1050993, AT and TT at rs4659743, GG at rs3768142, and GT and TT at rs3820571 were associated with a decreased risk of VSD (P<0.05). The variations at rs6668344 demonstrated an antagonistic multiplicative interaction with folic acid supplementation in relation to VSD (P<0.05). CONCLUSIONS: Maternal MTR gene polymorphisms significantly correlate with the incidence of VSD in offspring. Mothers with variations at rs6668344 can decrease the susceptibility to VSD in their offspring by supplementing with folic acid during the periconceptional period, suggesting the importance of periconceptional folic acid supplementation in genetically at-risk populations to prevent VSD in offspring.


Asunto(s)
5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa , Suplementos Dietéticos , Ácido Fólico , Defectos del Tabique Interventricular , Humanos , Ácido Fólico/administración & dosificación , Femenino , Defectos del Tabique Interventricular/genética , 5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/genética , Estudios de Casos y Controles , Lactante , Adulto , Embarazo , Polimorfismo Genético , Masculino , Polimorfismo de Nucleótido Simple
19.
J Nanobiotechnology ; 22(1): 485, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39138462

RESUMEN

Nanozymes are promising antimicrobials, as they produce reactive oxygen species (ROS). However, the intrinsic lack of selectivity of ROS in distinguishing normal flora from pathogenic bacteria deprives nanozymes of the necessary selectivities of ideal antimicrobials. Herein, we exploit the physiological conditions of bacteria (high alkaline phosphatase (ALP) expression) using a novel CuO nanoparticle (NP) nanoenzyme system to initiate an ALP-activated ROS prodrug system for use in the on-demand precision killing of bacteria. The prodrug strategy involves using 2-phospho-L-ascorbic acid trisodium salt (AAP) that catalyzes the ALP in pathogenic bacteria to generate ascorbic acid (AA), which is converted by the CuO NPs, with intrinsic ascorbate oxidase- and peroxidase-like activities, to produce ROS. Notably, the prodrug system selectively kills Escherichia coli (pathogenic bacteria), with minimal influence on Staphylococcus hominis (non-pathogenic bacteria) due to their different levels of ALP expression. Compared to the CuO NPs/AA system, which generally depletes ROS during storage, CuO NPs/AAP exhibits a significantly higher stability without affecting its antibacterial activity. Furthermore, a rat model is used to indicate the applicability of the CuO NPs/AAP fibrin gel in wound disinfection in vivo with negligible side effects. This study reveals the therapeutic precision of this bifunctional tandem nanozyme platform against pathogenic bacteria in ALP-activated conditions.


Asunto(s)
Fosfatasa Alcalina , Antibacterianos , Cobre , Desinfección , Escherichia coli , Profármacos , Especies Reactivas de Oxígeno , Cobre/química , Cobre/farmacología , Animales , Profármacos/farmacología , Profármacos/química , Fosfatasa Alcalina/metabolismo , Ratas , Antibacterianos/farmacología , Antibacterianos/química , Escherichia coli/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Desinfección/métodos , Ácido Ascórbico/farmacología , Ácido Ascórbico/química , Ácido Ascórbico/análogos & derivados , Nanopartículas del Metal/química , Ratas Sprague-Dawley , Masculino
20.
Poult Sci ; 103(10): 104064, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39106704

RESUMEN

Coccidiosis, caused by a protozoan parasite of the genus Eimeria, is one of the most severe contagious parasite diseases affecting the poultry industry worldwide. Using phytogenics to prevent chicken coccidiosis is a strategy aimed at combating the increasing issue of drug-resistant strains of Eimeria spp. This study demonstrates the anticoccidial activities of a medicinal herb, Trifolium pratense (TP) powder, and its ethanolic extract (designated TPE) against Eimeria spp. TPE exhibited significant suppressive activity against E. maxima oocyst sporulation and E. tenella sporozoite invasion and reproduction in Madin-Darby bovine kidney cells. Furthermore, administration of basal chicken diets containing TP powder or TPE to Eimeria-infected chickens significantly reduced the output of oocysts and severity of intestinal lesions. Dietary supplementation with TP significantly improved relative weight gain in E. tenella- and E. acervulina-infected chickens, while there was no significant improvement in E. maxima-infected chickens. The anticoccidial activities of TP and TPE on E. acervulina, E. tenella and E. maxima were further supported by anticoccidial index scores, which showed greater efficacy than those of amprolium, a commercial coccidiostat used in poultry. TP supplementation positively impacted the primary metabolism of chickens challenged with E. tenella or E. acervulina. The chemical fingerprints of TPE were established using liquid column chromatography; TPE contained 4 major compounds: ononin, sissotrin, formononetin, and biochanin A. In addition, various spectrometric methods were used to ensure the batch-to-batch consistency of TP/TPE. In conclusion, T. pratense is demonstrated to be a novel phytogenic supplement that can be used to control Eimeria-induced coccidiosis in chickens.


Asunto(s)
Coccidiosis , Coccidiostáticos , Extractos Vegetales , Enfermedades de las Aves de Corral , Trifolium , Trifolium/química , Suplementos Dietéticos , Coccidiostáticos/administración & dosificación , Coccidiostáticos/química , Coccidiostáticos/farmacología , Eimeria/efectos de los fármacos , Coccidiosis/tratamiento farmacológico , Coccidiosis/veterinaria , Pollos , Animales , Enfermedades de las Aves de Corral/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Masculino , Intestinos/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos
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