Virtual Screening of GLP-1-Secreting Peptides from Pea Protein Hydrolysates via Peptide Transporter 1 (PepT1) Activation-Based Molecular Docking.

Dietary proteins regulate glucose homeostasis via intestinal protein sensing-induced glucagon-like peptide 1 (GLP-1) secretion. However, the reported GLP-1-secreting peptides derived from dietary proteins are few, and studies regarding GLP-1-secreting peptide identification by traditional separation and purification methods are laborious. Herein, we have rapidly virtual-screened two GLP-1 secreting peptides from pea protein hydrolysates (PPHs) by peptidomic analysis and molecular docking with peptide transporter 1 (PepT1). PPH-stimulated GLP-1 secretion decreased after adding the PepT1 antagonist 4-aminobenzoic acid (4-AMBA), indicating that PepT1 activation was involved in PPH-induced GLP-1 secretion in NCI-H716 cells. Subsequently, 307 tripeptides in PPHs were obtained through peptidomic analysis. Among them, two GLP-1-secreting peptides, FLR and LRW, were identified via PepT1 activation-based molecular docking. FLR and LRW (1 mg/mL) increased GLP-1 levels to 170.20% ± 27.83% and 272.37% ± 45.96%, respectively (p < 0.05). More importantly, molecular docking implied that the interactions between peptides and the active center of PepT1 (especially Glu595, Asn329, and Asn171 in the N-pocket and Arg27 in the C-pocket) were crucial for peptide activity in stimulating GLP-1 secretion. Our study suggested that the combination of peptidomics and PepT1 activation-based molecular docking is a promising approach for identification of GLP-1-secreting peptides.

Synergistic effect of gellan gum and guar gum on improving the foaming properties of soy protein isolate-based complexes: Interaction mechanism and interfacial behavior.

Interactions among multi-component play a critical role in modulating the foaming properties of aerated foods. This study evaluated the mechanisms of synergistic improvement of gellan gum (GEG) and guar gum (GUG) on the foaming properties of soy protein isolate (SPI)-based complex. The results showed that the GEG/GUG ratio was closely related to the intermolecular interactions of SPI-based ternary complex and the dynamical changing of its foaming properties. The SPI/GEG/GUG ternary complex with a GEG/GUG ratio of 2/3 exhibited the highest foamability (195 %) and comparable foam stability (99.17 %), which were 32.95 % and 2.99 % higher than that of SPI/GEG binary complex. At this ratio, GUG promoted the interactions between SPI and GEG, and bound to complex's surface through hydrogen bonding, resulting in the increase of particle size and surface charge, and the decrease of surface hydrophobicity. Although this reduced the diffusion of complex onto the air/water interface, it increased permeation rate and molecular rearrangement behavior, which were the potential mechanisms to improve the foaming properties. Additionally, the synergistic effect of GEG and GUG also enhanced the elastic strength and solid characteristics of foam systems. This study provided a theoretical guidance for the targeted modulation of foaming properties of multi-component aerated foods.

A novel rat model of cerebral small vessel disease based on vascular risk factors of hypertension, aging, and cerebral hypoperfusion.

Cerebral small vessel disease (CSVD) is a major cause of vascular cognitive impairment and functional loss in elderly patients. Progressive remodeling of cerebral microvessels due to arterial hypertension or other vascular risk factors, such as aging, can cause dementia or stroke. Typical imaging characteristics of CSVD include cerebral microbleeds (CMB), brain atrophy, small subcortical infarctions, white matter hyperintensities (WMH), and enlarged perivascular spaces (EPVS). Nevertheless, no animal models that reflect all the different aspects of CSVD have been identified. Here, we generated a new CSVD animal model using D-galactose (D-gal) combined with cerebral hypoperfusion in spontaneously hypertensive rats (SHR), which showed all the hallmark pathological features of CSVD and was based on vascular risk factors. SHR were hypodermically injected with D-gal (400 mg/kg/d) and underwent modified microcoil bilateral common carotid artery stenosis surgery. Subsequently, neurological assessments and behavioral tests were performed, followed by vascular ultrasonography, electron microscopy, flow cytometry, and histological analyses. Our rat model showed multiple cerebrovascular pathologies, such as CMB, brain atrophy, subcortical small infarction, WMH, and EPVS, as well as the underlying causes of CSVD pathology, including oxidative stress injury, decreased cerebral blood flow, structural and functional damage to endothelial cells, increased blood-brain barrier permeability, and inflammation. The use of this animal model will help identify new therapeutic targets and subsequently aid the development and testing of novel therapeutic interventions. Main process of the study: Firstly, we screened for optimal conditions for mimicking aging by injecting D-gal into rats for 4 and 8 weeks. Subsequently, we performed modified microcoil BCAS intervention for 4 and 8 weeks in rats to screen for optimal hypoperfusion conditions. Finally, based on these results, we combined D-gal for 8 weeks and modified microcoil BCAS for 4 weeks to explore the changes in SHR.

Spatiotemporal evolution and key driver analysis of ozone pollution from the perspectives of spatial spillover and path-dependence effects in China.

In recent years, ozone (O3) has emerged as the primary air pollutant in China, superseding PM2.5. Previous studies have concentrated on the spatiotemporal variation of ozone pollution, the analysis of its sources and drivers, as well as its environmental impacts and health benefits. Since ozone pollution can be dynamically transferred through industrial activities and meteorological factors, it is crucial to scientifically identify the spatial spillover and path-dependent effects of ozone pollution in China. However, existing studies have not yet addressed this issue. Therefore, we investigate the spatiotemporal evolution and the spatial spillover of ozone pollution by means of the exploratory spatial data analysis (ESDA) using panel data of 30 Chinese provinces from 2013 to 2020 in this study. The dynamic spatial Durbin model (SDM) was employed to reveal the key drivers of ozone pollution from the perspectives of spatial spillover and path-dependence effects. The direct and spillover effects of each driver on ozone pollution are systematically analyzed. The results show that from 2013 to 2020 ozone concentrations followed a fluctuating upward trend at national and provincial scales. Ozone pollution presented significant spatial spillover and path dependence effects. The direct effects indicated that economic growth, technological level, industrial structure, energy structure, ventilation coefficient, relative humidity and precipitation were the key drivers of local ozone pollution. The spillover effects indicated that population density, technology level, industrial structure, environmental regulations, ventilation coefficient, sunshine hours and relative humidity had significant spatial spillover effects on ozone pollution of surrounding regions. These findings will contribute to the understanding of the spatial spillover and path-dependent effects of O3 pollution, and provide scientific guidance for regional synergy and long-term ozone control policies in China.

Related barriers to using HIV pre-exposure prophylaxis among MSM: A multicentre cross-sectional survey.

OBJECTIVE: The objective of this study was to gain insight into the barriers hindering the use of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) in five cities in China. METHODS: MSM were recruited via community-based organizations in an online "snowball" manner. Participants completed the questionnaire anonymously and shared it with key MSM peers (seeds) in five cities in China. Based on the results of univariate analysis, we used a structural equation model to analyse the role of PrEP knowledge awareness, PrEP counselling, and other behavioural variables on PrEP use. RESULTS: The study collected a total of 4223 valid questionnaires, and 18.2% of participants reported PrEP use. The results of the standardized total effects showed that the following paths were statistically significant (p < 0.05): from the age of first sex with men to PrEP knowledge awareness (ß = -0.113) and PrEP use (ß = 0.042); from high-risk sexual behaviour scores to PrEP counselling (ß = 0.039) and PrEP use (ß = 0.103); from the number of HIV tests in the last year to PrEP knowledge awareness (ß = 0.034), PrEP counselling (ß = 0.170), and PrEP use (ß = 0.197); from the level of self-perceived risk of HIV infection to PrEP counselling (ß = -0.115); from PrEP knowledge awareness to PrEP use (ß = -0.049); and from PrEP counselling to PrEP use (ß = 0.420). CONCLUSIONS: The proportion of PrEP use among MSM was relatively low. Age at first sex with men, number of HIV tests, high-risk sexual behaviour, and PrEP counselling had a positive effect on PrEP use, whereas PrEP knowledge awareness had an inverse effect on PrEP use.

MR defecography in assessing stress urinary incontinence with or without symptomatic pelvic organ prolapse.

PURPOSE: Utilize magnetic resonance defecography (MRD) to analyze the primary pelvic floor dysfunctions in patients with stress urinary incontinence (SUI) associated with pelvic organ prolapse (POP), and in SUI patients with asymptomatic POP. METHOD: We performed MRD in both SUI and POP subjects. As a primary analysis, the functional MR parameters were compared between the isolated POP and POP combined SUI groups. As a secondary analysis, the functional MR data were compared between the POP combined SUI and the SUI with asymptomatic POP (isolated SUI) groups. RESULTS: MRD noted the main characteristics of SUI combined moderate or severe POP, including the shorter closed urethra length (1.87 cm vs. 2.50 cm, p < 0.001), more prevalent urethral hypermobility (112.31° vs. 85.67°, p = 0.003), bladder neck funneling (48.28% vs. 20.51%, p = 0.020), lower position of vesicourethral junction (2.11 cm vs. 1.67 cm, p = 0.030), and more severe prolapse of the posterior bladder wall (6.26 cm vs. 4.35 cm, p = 0.008). The isolated SUI patients showed the shortest length of the closed urethra (1.56 cm vs. 1.87 cm, p = 0.029), a larger vesicourethral angle (153.80° vs. 107.58°, p < 0.001), the more positive bladder funneling (84.85% vs. 48.28%, p = 0.002) and a special urethral opening sign (45.45% vs. 3.45%, p < 0.001). CONCLUSIONS: Patients with SUI accompanying POP primarily exhibit excessive urethral mobility and a shortened urethral closure. SUI patients with asymptomatic POP mainly show dysfunction of the urethra and bladder neck, characterized by the opening of the urethra and bladder neck and a shortened urethral closure.

Enhancing nitrogen removal in constructed wetlands: The role of influent substrate concentrations in integrated vertical-flow systems.

Recent advancements in constructed wetlands (CWs) have highlighted the imperative of enhancing nitrogen (N) removal efficiency. However, the variability in influent substrate concentrations presents a challenge in optimizing N removal strategies due to its impact on removal efficiency and mechanisms. Here we show the interplay between influent substrate concentration and N removal processes within integrated vertical-flow constructed wetlands (IVFCWs), using wastewaters enriched with NO3--N and NH4+-N at varying carbon to nitrogen (C/N) ratios (1, 3, and 6). In the NO3--N enriched systems, a positive correlation was observed between the C/N ratio and total nitrogen (TN) removal efficiency, which markedly increased from 13.46 ± 2.23% to 87.00 ± 2.37% as the C/N ratio escalated from 1 to 6. Conversely, in NH4+-N enriched systems, TN removal efficiencies in the A-6 setup (33.69 ± 4.83%) were marginally 1.25 to 1.29 times higher than those in A-3 and A-1 systems, attributed to constraints in dissolved oxygen (DO) levels and alkalinity. Microbial community analysis and metabolic pathway assessment revealed that anaerobic denitrification, microbial N assimilation, and dissimilatory nitrate reduction to ammonium (DNRA) predominated in NO3--N systems with higher C/N ratios (C/N ≥ 3). In contrast, aerobic denitrification and microbial N assimilation were the primary pathways in NH4+-N systems and low C/N NO3--N systems. A mass balance approach indicated denitrification and microbial N assimilation contributed 4.12-47.12% and 8.51-38.96% in NO3--N systems, respectively, and 0.55-17.35% and 7.83-33.55% in NH4+-N systems to TN removal. To enhance N removal, strategies for NO3--N dominated systems should address carbon source limitations and electron competition between denitrification and DNRA processes, while NH4+-N dominated systems require optimization of carbon utilization pathways, and ensuring adequate DO and alkalinity supply.

Restricted-Access Media Column Switching Online Solid-Phase Extraction UHPLC-MS/MS for the Determination of Seven Type B Trichothecenes in Whole-Grain Preprocessed Foods and Human Exposure Risk Assessment.

With increasing health awareness and the accelerating pace of life, whole-grain prepared foods have gained popularity due to their health benefits and convenience. However, the potential risk of type B trichothecene toxins has also increased, and these mycotoxins in such foods are rarely regulated. In this study, a quantitative method combining a single-valve dual-column automatic online solid-phase extraction system with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed for the first time using restricted-access media columns. This method can simultaneously determine trace residues of seven type B trichothecenes within 15 min. The method is convenient, sensitive (limit of detection and quantification of 0.05-0.6 µg/kg and 0.15-2 µg/kg, respectively), accurate (recovery rates of 90.3%-106.6%, relative standard deviation < 4.3%), and robust (>1000 times). The established method was applied to 160 prepared food samples of eight categories sold in China. At least one toxin was detected in 70% of the samples. Whole-wheat dumpling wrappers had the highest contamination rate (95%) and the highest total content of type B trichothecenes in a single sample (2077.3 µg/kg). Exposure risk assessment indicated that the contamination of whole-grain prepared foods has been underestimated. The total health risk index of whole-wheat dumpling wrappers, which are susceptible to deoxynivalenol, reached 136.41%, posing a significant threat to human health. Effective measures urgently need to be taken to control this risk.

Study on fingerprint and quantitative analysis of Verbena officinalis water extract by LC-MS and HPLC.

Verbena officinalis L. as a medical plant has been used to treat many diseases. However, the quality control underlying V. officinalis remains to be studied. HPLC fingerprint analysis and the qualitative and quantitative analysis of water extract from V. officinalis were carried out, and it was found that the quality varies according to habitat and batch. Verbenalin could be a crucial component in the quality evaluation of V. officinalis. This study contributes to better understanding of quality control for V. officinalis.

Ecological filter walls for efficient pollutant removal from urban surface water.

Urban surface water pollution poses significant threats to aquatic ecosystems and human health. Conventional nitrogen removal technologies used in urban surface water exhibit drawbacks such as high consumption of carbon sources, high sludge production, and focus on dissolved oxygen (DO) concentration while neglecting the impact of DO gradients. Here, we show an ecological filter walls (EFW) that removes pollutants from urban surface water. We utilized a polymer-based three-dimensional matrix to enhance water permeability, and emergent plants were integrated into the EFW to facilitate biofilm formation. We observed that varying aeration intensities within the EFW's aerobic zone resulted in distinct DO gradients, with an optimal DO control at 3.19 ± 0.2 mg L-1 achieving superior nitrogen removal efficiencies. Specifically, the removal efficiencies of total organic carbon, total nitrogen, ammonia, and nitrate were 79.4%, 81.3%, 99.6%, and 79.1%, respectively. Microbial community analysis under a 3 mg L-1 DO condition revealed a shift in microbial composition and abundance, with genera such as Dechloromonas, Acinetobacter, unclassified_f__Comamonadaceae, SM1A02 and Pseudomonas playing pivotal roles in carbon and nitrogen elimination. Notably, the EFW facilitated shortcut nitrification-denitrification processes, predominantly contributing to nitrogen removal. Considering low manufacturing cost, flexible application, small artificial trace, and good pollutant removal ability, EFW has promising potential as an innovative approach to urban surface water treatment.

Tetris-inspired detector with neural network for radiation mapping.

Radiation mapping has attracted widespread research attention and increased public concerns on environmental monitoring. Regarding materials and their configurations, radiation detectors have been developed to identify the position and strength of the radioactive sources. However, due to the complex mechanisms of radiation-matter interaction and data limitation, high-performance and low-cost radiation mapping is still challenging. Here, we present a radiation mapping framework using Tetris-inspired detector pixels. Applying inter-pixel padding for enhancing contrast between pixels and neural networks trained with Monte Carlo (MC) simulation data, a detector with as few as four pixels can achieve high-resolution directional prediction. A moving detector with Maximum a Posteriori (MAP) further achieved radiation position localization. Field testing with a simple detector has verified the capability of the MAP method for source localization. Our framework offers an avenue for high-quality radiation mapping with simple detector configurations and is anticipated to be deployed for real-world radiation detection.

Anti-aging effect of peptides on Caenorhabditis elegans: a meta-analysis.

BACKGROUND: Recently, peptides have been studied in Caenorhabditis elegans for anti-aging research. Due to the lack of sufficient evidence, we conducted this meta-analysis focusing on the anti-aging effect of peptides in C. elegans to provide more convincing evidence. RESULTS: A literature search in PubMed, SCOUPUS, and Web of Science databases yielded 2879 articles. After removing duplicates and based on inclusion criteria and STAIR checklist quality assessment, nine articles were selected. Data extraction and analysis showed that, compared to the control group without peptide intervention, peptide supplementation significantly reduced nematode mortality risk [hazard ratio = 0.54, 95% confidence interval (CI) = 0.47, 0.62; P < 0.05], significantly increased the pharyngeal pumping rate [standardized mean difference (SMD) = 1.64, 95% CI = 0.87, 2.41; P < 0.05], bending frequency (SMD = 1.67, 95% CI = 1.16, 2.18; P < 0.05), and significantly decreased the accumulation of lipofuscin levels within nematodes (SMD = -4.48, 95% CI = -6.85, -2.12; P < 0.05). Additionally, subgroup analysis showed that doses ranging from 0.1 to 1 mg/mL (HR = 0.50, 95% CI = 0.38, 0.65; P < 0.05) displayed better anti-aging effects compared to other dose ranges. CONCLUSION: The findings suggest that peptides can significantly extend the lifespan of C. elegans under normal circumstances and improve three indicators of healthy life. More importantly, subgroup analysis revealed that a dosage of 0.1-1 mg/mL demonstrated superior anti-aging effects. This meta-analysis provides more convincing evidence that peptides can play an anti-aging role in C. elegans. © 2024 Society of Chemical Industry.

Potassium peroxoborate: A sustained-released reactive oxygen carrier with enhanced PAHs contaminated soil remediation performance.

Seeking for a safe, efficient, inexpensive, and eco-friendly oxidizer is always a big challenge for in-situ chemical oxidation (ISCO) technology. This study adopted the potassium peroxoborate (PPB), a novel peroxide, for soil remediation for the first time. PPB based chemical oxidation system (PPB-CO) could efficiently degrade polycyclic aromatic hydrocarbons (PAHs) without other reagents added, reaching 72.1 %, 64.2 %, and 50.0 % removal rates for naphthalene, phenanthrene, and pyrene after 24 h reaction, respectively. The superior total PAHs removal efficiency (60.6 %) was 3.6-4.7 times higher than that of other commercial peroxides (2Na2CO3•3H2O, CaO2, and H2O2). Mechanism analysis revealed that varieties of reactive oxygen species (ROS) can be generated by PPB through Fenton-like or non-Fenton routines, including H2O2, perborates species, O2•-, •OH, and 1O2. The sustainable generation of H2O2 reduced the disproportionation effect of H2O2 by 86 %, significantly improving the utilization rate. Moreover, sandbox experiments and actual contaminated soil remediation experiments verified the feasibility of PPB-CO in a real polluted site. This work provides a novel strategy for effectively soil remediation, highlighting the selection and application of new oxidants.

Understanding the foam stability mechanisms of complex formed by soy protein isolate and different charged polysaccharides: Air/water interfacial behavior and rheological characteristics.

This study evaluated the foaming properties, the dynamic adsorption behavior at the air/water (A/W) interface and the foam rheological characteristics of complexes formed by soy protein isolate (SPI) and different charged polysaccharides, including chitosan (CS), guar gum (GUG) and gellan gum (GEG). The results showed that the SPI/CS10 had the highest initial foam volume (26.67 mL), which were 3.89 %, 100.08 % and 70.19 % higher than that of single SPI, SPI/GUG and SPI/GEG complexes, respectively. Moreover, three charged polysaccharides could all significantly improve the foam stability of complexes. Among them, foams stabilized by SPI/GEG10 were the most stable that the foam volume slightly changed (approximately 1 mL) and no drainage occurred throughout the whole recording process. The interfacial behavior analysis showed that SPI/CS10 had higher diffusion (Kdiff) and rearrangement rate (KR) but lower penetration rate (KP) at the A/W interface compared with single SPI, while SPI/GUG10 and all SPI/GEG complexes showed higher KR and KP but lower Kdiff. In addition, SPI/CS10 was beneficial to concurrently enhance the elastic strength and solid-like behavior of foam system, while all SPI/GEG complexes could improve the elastic strength of foam system but was not conducive to the solid-like behavior.

A Nomogram for Predicting the Infectious Disease-specific Health Literacy of Older Adults in China.

PURPOSE: To identify the predictors of infectious disease-specific health literacy (IDSHL), and establish an easy-to-apply nomogram to predict the IDSHL of older adults. METHODS: This cross-sectional study included 380 older adults who completed the IDSHL, self-rated health, socio-demographic and other questionnaires. Logistic regression was used to identify the IDSHL predictors. Nomogram was used to construct a predictive model. RESULTS: Up to 70.1% of older adults had limited IDSHL. Age, education, place of residence, self-rated health, and Internet access were the important influencing factors of IDSHL. The established nomogram model showed high accuracy (receiver operating characteristic curve: 0.848). CONCLUSIONS: The IDSHL of Chinese older adults was significantly deficient. The constructed nomogram is an intuitive tool for IDSHL prediction that can not only contribute toward rapid screening of high-risk older adults with limited IDSHL but also provide guidance for healthcare providers to develop prevention strategies for infectious diseases.

Roles of Sirt1 and its modulators in diabetic microangiopathy: A review.

Diabetic vascular complications include diabetic macroangiopathy and diabetic microangiopathy. Diabetic microangiopathy is characterised by impaired microvascular endothelial function, basement membrane thickening, and microthrombosis, which may promote renal, ocular, cardiac, and peripheral system damage in diabetic patients. Therefore, new preventive and therapeutic strategies are urgently required. Sirt1, a member of the nicotinamide adenine dinucleotide-dependent histone deacetylase class III family, regulates different organ growth and development, oxidative stress, mitochondrial function, metabolism, inflammation, and aging. Sirt1 is downregulated in vascular injury and microangiopathy. Moreover, its expression and distribution in different organs correlate with age and play critical regulatory roles in oxidative stress and inflammation. This review introduces the background of diabetic microangiopathy and the main functions of Sirt1. Then, the relationship between Sirt1 and different diabetic microangiopathies and the regulatory roles mediated by different cells are described. Finally, we summarize the modulators that target Sirt1 to ameliorate diabetic microangiopathy as an essential preventive and therapeutic measure for diabetic microangiopathy. In conclusion, targeting Sirt1 may be a new therapeutic strategy for diabetic microangiopathy.

The role of inflammation in silicosis.

Silicosis is a chronic illness marked by diffuse fibrosis in lung tissue resulting from continuous exposure to SiO2-rich dust in the workplace. The onset and progression of silicosis is a complicated and poorly understood pathological process involving numerous cells and molecules. However, silicosis poses a severe threat to public health in developing countries, where it is the most prevalent occupational disease. There is convincing evidence supporting that innate and adaptive immune cells, as well as their cytokines, play a significant role in the development of silicosis. In this review, we describe the roles of immune cells and cytokines in silicosis, and summarize current knowledge on several important inflammatory signaling pathways associated with the disease, aiming to provide novel targets and strategies for the treatment of silicosis-related inflammation.

Serum high mobility group box 1 as a potential biomarker for the progression of kidney disease in patients with type 2 diabetes.

Background: As a damage-associated molecular pattern protein, high mobility group box 1 (HMGB1) is associated with kidney and systemic inflammation. The predictive and therapeutic value of HMGB1 as a biomarker has been confirmed in various diseases. However, its value in diabetic kidney disease (DKD) remains unclear. Therefore, this study aimed to investigate the correlation between serum and urine HMGB1 levels and DKD progression. Methods: We recruited 196 patients with type 2 diabetes mellitus (T2DM), including 109 with DKD and 87 T2DM patients without DKD. Additionally, 60 healthy participants without T2DM were also recruited as controls. Serum and urine samples were collected for HMGB1 analysis. Simultaneously, tumor necrosis factor receptor superfamily member 1A (TNFR-1) in serum and kidney injury molecule (KIM-1) in urine samples were evaluated for comparison. Results: Serum and urine HMGB1 levels were significantly higher in patients with DKD than in patients with T2DM and healthy controls. Additionally, serum HMGB1 levels significantly and positively correlated with serum TNFR-1 (R 2 = 0.567, p<0.001) and urine KIM-1 levels (R 2 = 0.440, p<0.001), and urine HMGB1 has a similar correlation. In the population with T2DM, the risk of DKD progression increased with an increase in serum HMGB1 levels. Multivariate logistic regression analysis showed that elevated serum HMGB1 level was an independent risk factor for renal function progression in patients with DKD, and regression analysis did not change in the model corrected for multiple variables. The restricted cubic spline depicted a nonlinear relationship between serum HMGB1 and renal function progression in patients with DKD (p-nonlinear=0.007, p<0.001), and this positive effect remained consistent across subgroups. Conclusion: Serum HMGB1 was significantly correlated with DKD and disease severity. When the HMGB1 level was ≥27 ng/ml, the risk of renal progression increased sharply, indicating that serum HMGB1 can be used as a potential biomarker for the diagnosis of DKD progression.

Angiographic demonstration of a cutoff sign as an unfavorable prognostic indicator for patients with acute ischemic stroke undergoing mechanical thrombectomy.

OBJECTIVES: The aim was to investigate whether the angiographic demonstration of a cutoff sign on the initial angiogram could predict recanalization and prognosis in acute ischemic stroke patients treated by endovascular thrombectomy. METHODS: The angiographic and clinical data of patients who underwent endovascular treatment from October 2018 to April 2023 were retrospectively reviewed. The pretreatment angiographic appearance of the thrombus's proximal part was assessed and classified as either the cutoff sign (+) or (-). Patients' baseline characteristics and angiographic and clinical outcomes between the two groups were analyzed using propensity score matching. Then, the two commonly used techniques, stent retrieval and contact aspiration, were compared in terms of successful reperfusion and clinical outcome in patients with the cutoff sign. RESULTS: The cutoff sign was observed in 77 (36.2%) of 213 patients. Patients with the cutoff sign were younger and were less likely to have involvement of the anterior circulation. Compared with the cutoff sign (-) group, the cutoff sign (+) group had a significantly longer procedure time (103 versus 80 min, P =0.002) and a lower percentage of 3-month good functional outcomes (18.2% versus 36%, P =0.006). After propensity score matching, the procedure time (100 versus 75 min, P =0.002) and the 3-month good outcome (19.2% versus 41.4%, P =0.004) remained significantly different. No significant differences were observed in the radiological (OR 0.758, 95% CI 0.157 to 3.658; P =0.730) and clinical (OR 0.747, 95% CI 0.147 to 3.787; P =0.725) outcomes between the two techniques. CONCLUSIONS: The cutoff sign might be an unfavorable prognostic indicator in patients undergoing mechanical thrombectomy, and the efficacy of mechanical thrombectomy techniques does not differ in patients positive for the cutoff sign.

Sirtuins in kidney diseases: potential mechanism and therapeutic targets.

Sirtuins, which are NAD+-dependent class III histone deacetylases, are involved in various biological processes, including DNA damage repair, immune inflammation, oxidative stress, mitochondrial homeostasis, autophagy, and apoptosis. Sirtuins are essential regulators of cellular function and organismal health. Increasing evidence suggests that the development of age-related diseases, including kidney diseases, is associated with aberrant expression of sirtuins, and that regulation of sirtuins expression and activity can effectively improve kidney function and delay the progression of kidney disease. In this review, we summarise current studies highlighting the role of sirtuins in renal diseases. First, we discuss sirtuin family members and their main mechanisms of action. We then outline the possible roles of sirtuins in various cell types in kidney diseases. Finally, we summarise the compounds that activate or inhibit sirtuin activity and that consequently ameliorate renal diseases. In conclusion, targeted modulation of sirtuins is a potential therapeutic strategy for kidney diseases. Video Abstract.