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CO poisoning in Pt-based anode catalysts significantly hampers the proton exchange membrane fuel cell (PEMFC) performance. Despite great advances in CO-tolerant catalysts, their effectiveness is often limited to fundamental three-electrode systems, which is inadequate for practical PEMFC applications. Herein, we present a straightforward thermal oxidation strategy for constructing a Ru oxide blocking layer on commercial PtRu/C through a one-step Ru-segregation-and-oxidation process. The resulting 0.7 nm thick Ru oxide layer effectively inhibits CO adsorption while maintaining hydrogen oxidation activity. PtRu@RuO2/C demonstrates exceptional CO tolerance, enduring 1% CO in rotating disk electrode tests, an â¼10-fold improvement compared to that of PtRu/C. Crucially, it retains high HOR activity and CO tolerance in PEMFC, with negligible polarization curve loss in the presence of 100 ppm CO. Notably, 85% HOR activity is retained after a 4 h stability test. This enhancement contributes to the Ru oxide layer decelerating CO adsorption kinetics, rather than promoting CO oxidation via the classic bifunctional mechanism.
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Frailty is a condition that is frequently observed among patients undergoing dialysis. Frailty is characterized by a decline in both physiological state and cognitive state, leading to a combination of symptoms, such as weight loss, exhaustion, low physical activity level, weakness, and slow walking speed. Frail patients not only experience a poor quality of life, but also are at higher risk of hospitalization, infection, cardiovascular events, dialysis-associated complications, and death. Frailty occurs as a result of a combination and interaction of various medical issues in patients who are on dialysis. Unfortunately, frailty has no cure. To address frailty, a multifaceted approach is necessary, involving coordinated efforts from nephrologists, geriatricians, nurses, allied health practitioners, and family members. Strategies such as optimizing nutrition and chronic kidney disease-related complications, reducing polypharmacy by deprescription, personalizing dialysis prescription, and considering home-based or assisted dialysis may help slow the decline of physical function over time in subjects with frailty. This review discusses the underlying causes of frailty in patients on dialysis and examines the methods and difficulties involved in managing frailty among this group.
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Fragilidade , Qualidade de Vida , Diálise Renal , Humanos , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Fragilidade/fisiopatologia , Diálise Renal/efeitos adversos , Idoso , Idoso Fragilizado , Polimedicação , Avaliação Geriátrica , Fatores de Risco , Falência Renal Crônica/terapia , Falência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/complicaçõesRESUMO
Tuberculosis (TB), characterized by high mortality and low diagnosis, is caused by a single pathogen, Mycobacterium tuberculosis (Mtb). Imaging tools that can be used to track Mtb without pre-labeling and to diagnose live Mtb in clinical samples can shorten the gap between bench and clinic, fuel the development of novel anti-TB drugs, strengthen TB prevention, and improve patient treatment. In this study, we report an unprecedented novel nitroreductase-responsive cyanine-based fluorescent probe (Cy3-NO2-tre) that rapidly and specifically labels Mtb and detects it in clinical samples. Cy3-NO2-tre generated fluorescence after activation by a specific nitroreductase, Rv3368c, which is conserved in the Mycobacteriaceae. Cy3-NO2-tre effectively imaged mycobacteria within infected host cells, tracked the infection process, and visualized Mycobacterium smegmatis being endocytosed by macrophages. Cy3-NO2-tre also detected Mtb in the sputum of patients with TB and exhibited excellent photostability. Furthermore, the Cy3-NO2-tre/auramine O percentage change within 7 ± 2 days post drug treatment in the sputum of inpatients was closely correlated with the reexamination results of the chest computed tomography, strongly demonstrating the clinical application of Cy3-NO2-tre as a prognostic indicator in monitoring the therapeutic efficacy of anti-TB drugs in the early patient care stage.
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Mycobacterium tuberculosis , Tuberculose , Humanos , Dióxido de Nitrogênio , Tuberculose/diagnóstico por imagem , Tuberculose/tratamento farmacológico , Antituberculosos/farmacologia , Mycobacterium smegmatis , Escarro/microbiologiaRESUMO
Systemic sclerosis (SSc) poses a significant challenge in autoimmunology, characterized by the development of debilitating fibrosis of skin and internal organs. The pivotal role of dysregulated T cells, notably the skewed polarization toward Th2 cells, has been implicated in the vascular damage and progressive fibrosis observed in SSc. In this study, we explored the underlying mechanisms by which cannabinoid receptor 2 (CB2) highly selective agonist HU-308 restores the imbalance of T cells to alleviate SSc. Using a bleomycin-induced SSc (BLM-SSc) mouse model, we demonstrated that HU-308 effectively attenuates skin and lung fibrosis by specifically activating CB2 on CD4+ T cells to inhibit the polarization of Th2 cells in BLM-SSc mice, which was validated by Cnr2-specific-deficient mice. Different from classical signaling downstream of G protein-coupled receptors (GPCRs), HU-308 facilitates the expression of SOCS3 protein and subsequently impedes the IL2/STAT5 signaling pathway during Th2 differentiation. The deficiency of SOCS3 partially mitigated the impact of HU-308. Analysis of a cohort comprising 80 SSc patients and 82 healthy controls revealed an abnormal elevation in the Th2/Th1 ratio in SSc patients. The proportion of Th2 cells showed a significant positive correlation with mRSS score and positivity of anti-Scl-70. Administration of HU-308 to PBMCs and peripheral CD4+ T cells from SSc patients led to the upregulation of SOCS3, which effectively suppressed the aberrantly activated STAT5 signaling pathway and the proportion of CD4+IL4+ T cells. In conclusion, our findings unveil a novel mechanism by which the CB2 agonist HU-308 ameliorates fibrosis in SSc by targeting and reducing Th2 responses. These insights provide a foundation for future therapeutic approaches in SSc by modulating Th2 responses.
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Diferenciação Celular , Modelos Animais de Doenças , Receptor CB2 de Canabinoide , Escleroderma Sistêmico , Transdução de Sinais , Proteína 3 Supressora da Sinalização de Citocinas , Células Th2 , Animais , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/patologia , Células Th2/imunologia , Camundongos , Receptor CB2 de Canabinoide/agonistas , Receptor CB2 de Canabinoide/metabolismo , Diferenciação Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Humanos , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Feminino , Janus Quinases/metabolismo , Masculino , Camundongos Knockout , Canabinoides/farmacologia , Canabinoides/uso terapêutico , Bleomicina , Agonistas de Receptores de Canabinoides/farmacologia , Agonistas de Receptores de Canabinoides/uso terapêutico , Pessoa de Meia-IdadeRESUMO
AIM: To analyse the association between serum bile acid (BA) profile and heart failure (HF) with preserved ejection fraction (HFpEF) in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: We enrolled 163 individuals with biopsy-proven MAFLD undergoing transthoracic echocardiography for any indication. HFpEF was defined as left ventricular ejection fraction >50% with at least one echocardiographic feature of HF (left ventricular diastolic dysfunction, abnormal left atrial size) and at least one HF sign or symptom. Serum levels of 38 BAs were analysed using ultra-performance liquid chromatography coupled with tandem mass spectrometry. RESULTS: Among the 163 patients enrolled (mean age 47.0 ± 12.8 years, 39.3% female), 52 (31.9%) and 43 (26.4%) met the HFpEF and pre-HFpEF criteria, and 38 serum BAs were detected. Serum ursodeoxycholic acid (UDCA) and hyocholic acid (HCA) species were lower in patients with HFpEF and achieved statistical significance after correction for multiple comparisons. Furthermore, decreases in glycoursodeoxycholic acid and tauroursodeoxycholic acid were associated with HF status. CONCLUSIONS: In this exploratory study, specific UDCA and HCA species were associated with HFpEF status in adults with biopsy-confirmed MAFLD.
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Ácidos e Sais Biliares , Insuficiência Cardíaca , Volume Sistólico , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/complicações , Ácidos e Sais Biliares/sangue , Volume Sistólico/fisiologia , Adulto , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Ecocardiografia , Biomarcadores/sangueRESUMO
Microfluidic technology has emerged as a powerful tool in studying arterial thrombosis, allowing researchers to construct artificial blood vessels and replicate the hemodynamics of blood flow. This technology has led to significant advancements in understanding thrombosis and platelet adhesion and aggregation. Microfluidic models have various types and functions, and by studying the fabrication methods and working principles of microfluidic chips, applicable methods can be selected according to specific needs. The rapid development of microfluidic integrated system and modular microfluidic system makes arterial thrombosis research more diversified and automated, but its standardization still needs to be solved urgently. One key advantage of microfluidic technology is the ability to precisely control fluid flow in microchannels and to analyze platelet behavior under different shear forces and flow rates. This allows researchers to study the physiological and pathological processes of blood flow, shedding light on the underlying mechanisms of arterial thrombosis. In conclusion, microfluidic technology has revolutionized the study of arterial thrombosis by enabling the construction of artificial blood vessels and accurately reproducing hemodynamics. In the future, microfluidics will place greater emphasis on versatility and automation, holding great promise for advancing antithrombotic therapeutic and prophylactic measures.
What is the context? To study the mechanism of arterial thrombosis, including the platelet adhesion and aggregation behavior and the coagulation process.Microfluidic technology is commonly used to study thrombosis. Microfluidic technology can simulate the real physiological environment on the microscopic scale in vitro, with high throughput, low cost, and fast speed.As an innovative experimental platform, microfluidic technology has made remarkable progress and has found applications in the fields of biology and medicine.What is new? This review summarizes the different fabrication methods of microfluidics and compares the advantages and disadvantages of these methods. Recent developments in microfluidic integrated systems and modular microfluidic systems have led to more diversified and automated microfluidic chips in the future.The different types and functions of microfluidic models are summarized. Platelet adhesion aggregation and coagulation processes, as well as arterial thrombus-related shear force changes and mechanical behaviors, were investigated by constructing artificial blood vessels and reproducing hemodynamics.Microfluidics can provide a basis for the development of personalized thrombosis treatment strategies. By analyzing the mechanism of action of existing drugs, using microfluidic technology for high-throughput screening of drugs and evaluating drug efficacy, more drug therapy possibilities can be developed.What is the impact?This review utilizes microfluidics to further advance the study of arterial thrombosis, and microfluidics is also expected to play a greater role in the biomedical field in the future.
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Substitutos Sanguíneos , Trombose , Humanos , Microfluídica/métodos , Plaquetas/patologia , Trombose/patologia , Adesividade PlaquetáriaRESUMO
Social working memory (WM) temporarily retains and manipulates various aspects of social information. Extensive research has highlighted impaired social cognitive functions in individuals with substance addiction. However, the specific deficit in social WM within this population remains notably understudied. Bridging this gap, we investigated social WM capacity using biological motion (BM) stimuli in methamphetamine (MA) abusers compared to an inmate control group, alongside contrasting these findings with their canonical WM deficits. Across two studies, we recruited female MA abusers (N = 80) undergoing post-isolation rehabilitation within a mandatory confinement circumstance. To ensure a pertinent comparison, we recruited female inmates (N = 80) subjected to comparable confinement. Results show substantial BM WM impairment in MA abusers, yet non-BM WM remains mostly intact. These findings highlight a pronounced social WM deficit in MA abusers, surpassing their canonical WM deficit relative to inmate controls. This suggests a distinct dissociation between social and canonical WM processing.
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Secondary hyperparathyroidism (SHPT) can progress to severe SHPT (sSHPT), which affects the survival rate and quality of life of patients. This retrospective cohort study investigated risk factors for sSHPT and the association between SHPT and mortality (all-cause and infection-related) among 771 clinically stable patients (421 male patients; mean age, 51.2 years; median dialysis vintage, 28.3 months) who underwent >3 months of regular peritoneal dialysis (PD) between January 2013 and March 2021. The sSHPT and non-sSHPT groups comprised 75 (9.7%) (median progression, 35 months) and 696 patients, respectively. sSHPT was defined as a serum intact parathyroid hormone (PTH) level >800 pg/mL observed three times after active vitamin D pulse therapy. The influence of sSHPT on the prognosis of and risk factors for sSHPT progression were evaluated using logistic and Cox regression analyses. After adjusting for confounding factors, higher (each 100-pg/mL increase) baseline PTH levels (95% confidence interval (CI) 1.206-1.649, p < .001), longer (each 1-year increase) dialysis vintages (95% CI 1.013-1.060, p = .002), higher concomitant diabetes rates (95% CI 1.375-10.374, p = .010), and lower (each 1-absolute unit decrease) Kt/V values (95% CI 0.859-0.984, p = .015) were independent risk factors for progression to sSHPT in patients on PD. During follow-up, 211 deaths occurred (sSHPT group, n = 35; non-sSHPT group, n = 176). The sSHPT group had significantly higher infection-related mortality rates than the non-sSHPT group (12.0% vs. 4.3%; p < .05), and sSHPT was associated with increased infection-related mortality. In conclusion, patients with sSHPT are at higher risk for death and infection-related mortality than patients without sSHPT.
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Hiperparatireoidismo Secundário , Falência Renal Crônica , Hormônio Paratireóideo , Diálise Peritoneal , Humanos , Masculino , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/sangue , Pessoa de Meia-Idade , Estudos Retrospectivos , Feminino , Diálise Peritoneal/efeitos adversos , Prognóstico , Fatores de Risco , Hormônio Paratireóideo/sangue , Adulto , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Falência Renal Crônica/mortalidade , Falência Renal Crônica/sangue , Progressão da Doença , Modelos de Riscos ProporcionaisRESUMO
OBJECTIVE: Malnutrition and inflammation are associated with mortality in peritoneal dialysis (PD) patients. Serum albumin and non-high-density lipoprotein cholesterol (non-HDL-C) are independently associated with mortality in PD patients. Combining albumin and non-HDL-C with mortality may be more plausible in clinical practice. METHODS: This retrospective cohort study included 1954 Chinese PD patients from 1 January 2009 to 31 December 2016. Kaplan-Meier curve was used to determine the relationship between albumin to non-HDL-C ratio and all-cause mortality. Cox regression analysis was applied to assess the independent predictive value while adjusting for confounding factors. Competitive risk analysis was used to examine the effects of other outcomes on all-cause mortality prognosis. RESULTS: In the 33-month follow-up period, there were 538 all-cause deaths. Kaplan-Meier analysis presented significant differences in all-cause mortality. Multivariate Cox regression showed that the risk of all-cause mortality was lower in the moderate group (9.36-12.79) (HR, 0.731; 95% CI, 0.593-0.902, p = 0.004) and the highest group (>12.79) (HR, 0.705; 95% CI, 0.565-0.879, p = 0.002) compared to the lowest group (≤9.36). Competitive risk analysis revealed significant differences for all-cause mortality (p < 0.001), while there was no statistical significance for other competing events. CONCLUSIONS: Low albumin to non-HDL-C ratio was associated with a high risk of all-cause mortality in PD patients. It may serve as a potential prognostic biomarker in PD patients.
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Diálise Peritoneal , Albumina Sérica , Humanos , Estudos Retrospectivos , ColesterolRESUMO
Low-light imaging capabilities are in urgent demand in many fields, such as security surveillance, night-time autonomous driving, wilderness rescue, and environmental monitoring. The excellent performance of SPAD devices gives them significant potential for applications in low-light imaging. This article presents a 64 (rows) × 128 (columns) SPAD image sensor designed for low-light imaging. The chip utilizes a three-dimensional stacking architecture and microlens technology, combined with compact gated pixel circuits designed with thick-gate MOS transistors, which further enhance the SPAD's photosensitivity. The configurable digital control circuit allows for the adjustment of exposure time, enabling the sensor to adapt to different lighting conditions. The chip exhibits very low dark noise levels, with an average DCR of 41.5 cps at 2.4 V excess bias voltage. Additionally, it employs a denoising algorithm specifically developed for the SPAD image sensor, achieving two-dimensional grayscale imaging under 6 × 10-4 lux illumination conditions, demonstrating excellent low-light imaging capabilities. The chip designed in this paper fully leverages the performance advantages of SPAD image sensors and holds promise for applications in various fields requiring low-light imaging capabilities.
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To investigate the clinical efficacy of acupuncture combined with biofeedback electrical stimulation on female stress urinary incontinence. Ninety patients diagnosed in a hospital between January 2020 and January 2021 were randomly divided into three groups (A, B and C). Group A was treated with biofeedback electrical stimulation, 3 times a week for 30 min for 15 times. Group B used acupuncture treatment, including Guanyuan, Qihai, Zhongji, Zusanli, Sanyinjiao and Yinlingquan, once a day, Monday-Friday, 30 min each, for a total of 10 times. Group C was treated with acupuncture combined with biofeedback electrical stimulation. All three groups were combined with pelvic floor muscle training. Following treatment, the changes in class I and II muscle fibre strength, ICI-Q-SF score and urine leakage in the 1-hour pad test were compared. Prior to treatment, there was no significant difference in the general data of the three patient groups, as well as class I and II muscle fibre strength, ICI-Q-SF score and 1-hour urinary pad test (P > 0.05). Following treatment, class I and II muscle fibre strength in groups A and C improved compared with before, with statistical significance (P < 0.05); there was no significant difference in group B (P > 0.05). In the three groups, ICI-Q-SF scores and 1-hour urinary pad test results were lower compared with before (P < 0.05), with those in group C better than those in groups A and B (P < 0.05). The treatment efficiency of the three patient groups was 86.7%, 83.3% and 96.7%, respectively. Combined acupuncture and biofeedback electrical stimulation can improve pelvic floor muscle strength, urine leakage and quality of life, and can be superior to biofeedback and acupuncture treatment alone.
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INTRODUCTION: Evidence has emerged that cardiometabolic multimorbidity (CMM) is associated with dementia, but the underlying mechanisms are poorly understood. METHODS: This population-based study included 5704 older adults. Of these, data were available in 1439 persons for plasma amyloid-ß (Aß), total tau, and neurofilament light chain (NfL) and in 1809 persons for serum cytokines. We defined CMM following two common definitions used in previous studies. Data were analyzed using general linear, logistic, and mediation models. RESULTS: The presence of CMM was significantly associated with an increased likelihood of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) (p < 0.05). CMM was significantly associated with increased plasma Aß40, Aß42, and NfL, whereas CMM that included visceral obesity was associated with increased serum cytokines. The mediation analysis suggested that plasma NfL significantly mediated the association of CMM with AD. DISCUSSION: CMM is associated with dementia, AD, and VaD in older adults. The neurodegenerative pathway is involved in the association of CMM with AD. HIGHLIGHTS: The presence of CMM was associated with increased likelihoods of dementia, AD, and VaD in older adults. CMM was associated with increased AD-related plasma biomarkers and serum inflammatory cytokines. Neurodegenerative pathway was partly involved in the association of CMM with AD.
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Whether adulteration exists is a difficult problem in the identification of traditional Chinese medicine(TCM). Bubali Cornu is mainly available in the medicinal material market in the form of buffalo horn silk or buffalo horn powder but lacks obvious identification characteristics, so there is a risk of adulteration. However, the method of identification of adulteration in Bubali Cornu is lacking at present. In order to ensure authenticity and identify adulteration of TCM Bubali Cornu, control the quality of TCM Bubali Cornu, and ensure the authenticity of clinical use, the DNA fingerprints of 43 batches of samples from pharmaceutical companies and medicinal material markets were identified, and the amplification primers of fluorescent DNA fingerprints of Bubali Cornu and Bovis Grunniens Cornu were screened. The DNA fingerprints of Bubali Cornu were obtained by fluorescent capillary typing. The identification effect of fluorescent capillary typing on different adulteration ratios was also tested. Two pairs of fluorescent STR typing primers, namely 16Sa and CRc, which can distinguish Bubali Cornu and Bovis Grunniens Cornu, were screened out, and a DNA fingerprint identification method was established. The 16Sa migration peaks of Bovis Grunniens Cornu and Bubali Cornu were 223.4-223.9 bp and 225.5-226.1 bp. The CRc migration peaks of Bovis Grunniens Cornu and Bubali Cornu were 518.8-524.8 bp and 535.9-542.5 bp. The peak height of the migration peak could be used for preliminary quantification of the adulterants with an adulteration ratio below 50%, and the quantitative results were similar to the adulteration ratio. In this study, a simple and quick universal DNA fingerprint method was established for the identification of Bubali Cornu and its adulterants, which could realize the identification of TCM Bubali Cornu and the semi-quantitative identification of the adulterants.
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Búfalos , Impressões Digitais de DNA , Contaminação de Medicamentos , Impressões Digitais de DNA/métodos , Animais , Búfalos/genética , Medicina Tradicional Chinesa , Cornos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análiseRESUMO
For heterojunction system, the lack of stable interfacial driving force and definite charge transfer channel makes the charge separation and transfer efficiency unsatisfactory. The photoreaction mechanism occurring at the interface also receives less attention. Herein, a 2D/2D Z-scheme junction BiOBr@NiFe-LDH with large-area contact featured by abundant interfacial hydrogen bonds and a strong interfacial electric field (IEF) is synthesized, and in-situ photoinduced metallic species assisting charge transfer mechanism is demonstrated. The hydrogen bonds between O atoms from BiOBr and H atoms from NiFe-LDH induce a significant interfacial charge redistribution, establishing a robust IEF. Notably, during photocatalytic reaction, Bi0 and Ni0 are in-situ isolated from BiOBr and NiFe-LDH in heterojunction, which separately act as electron transport mediator and electron trap to further accelerate charge transfer efficiency up to 71.2%. Theoretical calculations further demonstrate that the existence of Bi0 strengthens the IEF. Therefore, high-speed spatial charge separation is realized in Bi0/BiOBr@Ni0/NiFe-LDH, leading to a prominent photocatalytic activity with a tetracycline removal ratio of 88.3% within 7 minutes under visible-light irradiation and the presence of persulfate, far exceeding majority of photocatalysts reported previously. This study provides valid insights for designing hydrogen bonding heterojunction systems, and advances mechanistic understanding on in-situ photoreaction at interfaces.
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Organic solvent nanofiltration (OSN) plays important roles in pharmaceutical ingredients purification and solvent recovery. However, the low organic solvent permeance under cross-flow operation of OSN membrane hampers their industrial applications. Herein, we report the construction of coffee-ring structured membrane featuring high OSN permeance. A water-insoluble crystal monomer that dissolved in EtOH/H2O mixed solvent was designed to react with trimesoyl chloride via interfacial polymerization. Owing to the diffusion of EtOH to n-hexane, coffee-ring nanostructure on the support membrane appeared, which served as the template for construction of coffee-ring structured membrane. The optimal nanostructured membrane demonstrated 2.6-fold enhancement in the effective surface area with reduced membrane thickness. Resultantly, the membrane afforded a 2.7-fold enhancement in organic solvent permeance, e.g., ~13â LMH/bar for MeOH, without sacrificing the rejection ability. Moreover, due to the rigid monomer structure, the fabricated membrane shows distinctive running stability in active pharmaceutical ingredients purification and the ability for concentration of medicines.
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In recent years, preclinical research on diabetic kidney disease (DKD) has surged to the forefront of scientific and clinical attention. DKD has become a pervasive complication of type 2 diabetes. Given the complexity of its etiology and pathological mechanisms, current interventions, including drugs, dietary modifications, exercise, hypoglycemic treatments and lipid-lowering methods, often fall short in achieving desired therapeutic outcomes. Iridoids, primarily derived from the potent components of traditional herbs, have been the subject of long-standing research. Preclinical data suggest that iridoids possess notable renal protective properties; however, there has been no summary of the research on their efficacy in the management and treatment of DKD. This article consolidates findings from in vivo and in vitro research on iridoids in the context of DKD and highlights their shared anti-inflammatory activities in treating this condition. Additionally, it explores how certain iridoid components modify their chemical structures through the regulation of intestinal flora, potentially bolstering their therapeutic effects. This review provides a focused examination of the mechanisms through which iridoids may prevent or treat DKD, offering valuable insights for future research endeavors. Please cite this article as: Zhou TY, Tian N, Li L, Yu R. Iridoids modulate inflammation in diabetic kidney disease: A review. J Integr Med. 2024; 22(3): 210-222.
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Nefropatias Diabéticas , Iridoides , Nefropatias Diabéticas/tratamento farmacológico , Humanos , Iridoides/farmacologia , Iridoides/uso terapêutico , Animais , Inflamação/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicaçõesRESUMO
Key Clinical Message: CA of LVS premature beats complexes is difficult due to anatomical limitations. We report a patient with PVCs originating from the LVS region who was successfully ablated by ablation. Abstract: Catheter ablation (CA) of premature ventricular contractions (PVCs) arising from the left ventricular summit (LVS) presents technical challenges due to the regional anatomy and frequently intramural site of origin. Herein, we demonstrated a case of a successful CA, originating from the LVS region. We further discussed the detailed anatomical background and clinical feasibility of CA as an alternative ablation route for PVCs originating from the LVS.
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Intermittent hypoxia in patients with obstructive sleep apnea (OSA) hypopnea syndrome (OSAHS) is associated with pharyngeal cavity collapse during sleep. The effect of human umbilical cord mesenchymal stem cells (HUCMSCs) on OSA-induced oxidative damage in the genioglossus and whether nuclear factor erythroid 2-related factor 2 (Nrf2) or its upstream genes play a key role in this process remains unclear. This study aimed to identify the key factors responsible for oxidative damage during OSAHS through Nrf2 analysis and hypothesize the mechanism of HUCMSC therapy. We simulated OSA using an intermittent hypoxia model, observed the oxidative damage in the genioglossus and changes in Nrf2 expression during intermittent hypoxia, and administered HUCMSCs therapy. Nrf2 initially increased, then decreased, aggravating the oxidative damage in the genioglossus; Nrf2 protein content decreased during hypoxia. Using transcriptomics, we identified seven possible factors in HUCMSCs involved in ameliorating oxidative stress by Nrf2, of which DJ-1 and MEF2A, showing trends similar to Nrf2, were selected by polymerase chain reaction. HUCMSCs may reduce oxidative stress induced by intermittent hypoxia through Nrf2, and the possible upstream target genes in this process are MEF2A and DJ-1. Further studies are needed to verify these findings.
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Células-Tronco Mesenquimais , Apneia Obstrutiva do Sono , Humanos , Terapia Baseada em Transplante de Células e Tecidos , Hipóxia/metabolismo , Células-Tronco Mesenquimais/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Cordão Umbilical/metabolismoRESUMO
Hepatocellular carcinoma (HCC) is a significant contributor to global cancer-related deaths, leading to high mortality rates. However, the pathogenesis of HCC remains unclear. In this research, by the bioinformatics data analysis, we found that elevated CSTB expression correlated with advanced disease and predicted diminished overall survival (OS) in HCC patients. We subsequently verified the oncogenic role of CSTB as well as the potential underlying mechanisms in HCC through a series of in vitro experiments, such as CCK-8 assays, cloning assays, flow cytometry, Transwell assays, and western blotting. Our findings illustrated that the silencing of CSTB effectively suppressed cellular proliferation by inducing cell cycle arrest in the G2 phase and impaired HCC cell invasion and migration by stimulating epithelial-mesenchymal transition (EMT). Additionally, we analyzed the pathways enriched in HCC using RNA sequencing and found that the ERK/AKT/mTOR signaling pathway was related to increased CSTB expression in HCC. Finally, we confirmed the tumorigenic role of CSTB via in vivo experiments. Thus, our findings revealed that silencing CSTB inhibited the HCC progression via the ERK/AKT/mTOR signaling pathway, highlighting new perspectives for investigating the mechanisms of HCC.
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Domain Generalization (DG) focuses on the Out-Of-Distribution (OOD) generalization, which is able to learn a robust model that generalizes the knowledge acquired from the source domain to the unseen target domain. However, due to the existence of the domain shift, domain-invariant representation learning is challenging. Guided by fine-grained knowledge, we propose a novel paradigm Mask-Shift-Inference (MSI) for DG based on the architecture of Convolutional Neural Networks (CNN). Different from relying on a series of constraints and assumptions for model optimization, this paradigm novelly shifts the focus to feature channels in the latent space for domain-invariant representation learning. We put forward a two-branch working mode of a main module and multiple domain-specific sub-modules. The latter can only achieve good prediction performance in its own specific domain but poor predictions in other source domains, which provides the main module with the fine-grained knowledge guidance and contributes to the improvement of the cognitive ability of MSI. Firstly, during the forward propagation of the main module, the proposed MSI accurately discards unstable channels based on spurious classifications varying across domains, which have domain-specific prediction limitations and are not conducive to generalization. In this process, a progressive scheme is adopted to adaptively increase the masking ratio according to the training progress to further reduce the risk of overfitting. Subsequently, our paradigm enters the compatible shifting stage before the formal prediction. Based on maximizing semantic retention, we implement the domain style matching and shifting through the simple transformation through Fourier transform, which can explicitly and safely shift the target domain back to the source domain whose style is closest to it, requiring no additional model updates and reducing the domain gap. Eventually, the paradigm MSI enters the formal inference stage. The updated target domain is predicted in the main module trained in the previous stage with the benefit of familiar knowledge from the nearest source domain masking scheme. Our paradigm is logically progressive, which can intuitively exclude the confounding influence of domain-specific spurious information along with mitigating domain shifts and implicitly perform semantically invariant representation learning, achieving robust OOD generalization. Extensive experimental results on PACS, VLCS, Office-Home and DomainNet datasets verify the superiority and effectiveness of the proposed method.