Construction of a BiOI/ZnO heterojunction on biomass Juncus effusus fiber for photodegradation of organic pollutants.

Semiconductor heterojunction engineering and three-dimensional (3D) architecture construction have been considered highly desirable strategies to enhance photocatalytic performance. Herein, a BiOI/ZnO composite photocatalyst with a 3D flower-like architecture was successfully prepared, which was stably immobilized on three-dimensional porous lignocellulosic biomass Juncus effusus (JE) fiber. The outstanding photocatalytic performance of the BiOI/ZnO-JE fiber was confirmed by the degradation of tetracycline hydrochloride (TC, 90%), ciprofloxacin (CIP, 79%), and norfloxacin (NOR, 81%). The enhanced photocatalytic activities were mainly attributed to the synergistic absorption performance of the lignocellulosic JE and the effective transfer and separation of charges. Moreover, the hydroxyl (·OH) and superoxide radicals (·O2-) are the main reactive species in the photocatalytic process according to the analysis. This work may provide a novel perspective for constructing high-performance lignocellulosic-based photocatalytic materials.

Postinterventional Petechial Hemorrhage Associated With Poor Functional Outcome After Successful Recanalization Following Endovascular Therapy.

BACKGROUND AND OBJECTIVES: Endovascular therapy (EVT) has emerged as the standard for treating patients with acute ischemic stroke due to large vessel occlusion. The aim of this study was to investigate the relationship between early petechial hemorrhage and patient outcomes after successful EVT of anterior circulation. METHODS: We retrospectively analyzed multicenter data from 316 patients who underwent EVT for acute occlusion of anterior circulation. Patients were divided into petechial hemorrhage group and without hemorrhage group based on post-EVT head imaging. Logistical regression analysis was performed to determine independent predictors for petechial hemorrhage, and for petechial hemorrhage as a predictor of early neurological improvement, favorable outcome at 90 days (modified Rankin Scale 0-2), and 90-day mortality, with adjustment for all factors significantly associated with these endpoints in univariate regression to P < .10. RESULTS: Of 316 included patients with successful EVT, 49 (15.50%) had petechial hemorrhage. The petechial hemorrhage group showed less early neurological improvement (36.73% compared with 53.56%, P = .030), less favorable outcomes at 90 days (32.65% compared with 61.80%, P < .001, absolute risk difference 29.15%), and higher mortality at 90 days (28.57% compared with 10.49%, P = .001) then the group without hemorrhage. Petechial hemorrhage was inversely associated with favorable 90-day outcome (odds ratio = 0.415, 95% CI 0.206-0.835) and higher mortality rate at 90 days (odds ratio = 2.537, 95% CI 1.142-5.635) in multivariable regression but was not independently associated with early neurological improvement. CONCLUSION: In patients with anterior large vessel occlusion who underwent successful EVT, petechial hemorrhage was associated with poor functional outcome and 90-day mortality when adjusted for complete recanalization, pre-EVT National Institute of Health Stroke Scale/Score, and Alberta Stroke Program Early Computed Tomography Score. Despite the relatively lower rate of a favorable 90-day outcome with petechial hemorrhage compared with no petechial hemorrhage, the absolute rate of a favorable outcome exceeds the natural history of medical management for this condition.

The role of reactive oxygen species in regulation of the plasma membrane H +-ATPase activity in Masson pine (Pinus massoniana Lamb.) roots responding to acid stress.

To understand the role of reactive oxygen species (ROS) in regulation of the plasma membrane (PM) H+-ATPase in acid-stressed Masson pine roots, different acidity (pH 6.6 as the control, pH 5.6, and pH 4.6) of simulated acid rain (SAR) added with and without external chemicals [H2O2, enzyme inhibitors, and ROS scavenger] was prepared. After 30 days of SAR exposure, the plant morphological phenotype attributes, levels of cellular ROS and lipid peroxidation, enzymatic activities of antioxidants, PM nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and PM H+-ATPase activity in pine seedlings were measured. Compared to the control, the growth of pine seedlings exposed to SAR in the presence or absence of H2O2 was well-maintained, but the application of Na3VO4, 1,3-Dimethyl-2-thiourea, N, N-dimethylthiourea (DMTU), and diphenyleneiodonium chloride (DPI) caused a substantial growth inhibition. In addition, SAR exposure, SAR with H2O2 treatment, and SAR with Na3VO4 treatment increased the cellular H2O2 content, O2·- content, and malondialdehyde (MDA) content, while the use of DMTU and DPI lead to relatively low levels. Similarly, the enzymatic activities of antioxidants, PM NADPH oxidase, and PM H+-ATPase in acid stressed pine seedlings elevated with the increasing acidity. A significant stimulation of these enzymatic activities obtained from SAR with H2O2 treatment was observed, whereas which decreased obviously with the addition of Na3VO4, DMTU, and DPI (P < 0.05). Moreover, a positive correlation was found between plant morphological attributes and the PM H+-ATPase activity (P < 0.05). Besides, the PM H+-ATPase activity positively correlated with the cellular ROS contents and the enzymatic activities of antioxidants and PM NADPH oxidase (P < 0.05). Therefore, the PM H+-ATPase is instrumental in the growth of pine seedlings resisting to acid stress by enhancing its activity. The process involves the signaling transduction of cellular ROS and coordination with PM NADPH oxidase.

Visible Light [2 + 2] Cycloadditions of Thermoresponsive Dendronized Styryltriazines To Exhibit Tunable Microconfinement.

Visible light-triggered photochemical reactions in aqueous media are highly valuable to tailor molecular structures and properties in an ecofriendly manner. Here we report visible light-induced catalyst-free [2 + 2] cycloadditions of thermoresponsive dendronized styryltriazines, which show tunable microconfinement to guest dyes in aqueous media. These dendronized styryltriazines are constituted of conjugated mono- or tristyryltriazines, which carry hydrophilic dendritic oligoethylene glycol (OEG) pendants. They underwent efficient [2 + 2] cycloadditions to form dendronized cyclobutane dimers or oligomers in water through irradiation with visible light of 400 nm, and their cycloaddition behavior was dominated by dendritic architectures and solvent conditions. Dendronization with dendritic OEGs also afforded them characteristic thermoresponsive properties with tunable phase transition temperatures in the range 36-65 °C, which can be further modulated through photocycloaddition of styryltriazine chromophores. Importantly, dendronized styryltriazines can form tunable microenvironments in aqueous media, which encapsulate hydrophobic solvatochromic Nile red to exhibit variable photophysical properties. The encapsulated guest dye can be simultaneously released through noninvasive visible light-induced [2 + 2] cycloaddition reactions.

Sex Differences in Outcomes after Endovascular Thrombectomy for Patients with Acute Ischemic Stroke.

INTRODUCTION: Endovascular thrombectomy (EVT) is the standard of care for patients with large-vessel occlusion acute ischemic stroke (AIS). There may be differing recanalization effectiveness based on patients' sex, and understanding such variations can improve patient outcomes by adjusting for differences. We aimed to assess the sex differences in outcome after EVT for patients with AIS. METHODS: We retrospectively analyzed 250 consecutive AIS patients who underwent EVT from July 2019 to February 2022 across two large comprehensive tertiary care stroke centers in China. Outcomes of male patients were compared to females, where poor outcome was defined as a modified Rankin score (mRS) of 3-6 at 90 days. RESULTS: Male patients had higher rates of symptomatic intracranial hemorrhage (sICH) (12.50% vs. 4.05%, p = 0.042) and higher hospitalization costs (114,541.08 vs. 105,790.27 RMB, p = 0.024). Male patients also had a longer median onset-to-needle time (ONT) (146.00 [104.00, 202.00] versus 120.00 [99.25, 144.75], p = 0.026). However, there were no differences in hospitalization length (p = 0.251), 90-day favorable outcome (p = 0.952), and 90-day mortality (p = 0.931) between the sexes. CONCLUSION: Female patients had lower hospitalization costs and sICH rates than males after EVT for AIS. Identifying such differences and implementing measures, including adaptations to workflow optimization, would help to reduce the ONT and last known normal-to-puncture time seen in males to improve patient outcomes. Despite such variations, favorable outcomes and mortality are similar in female and male AIS patients.

c-Cbl induced podocin ubiquitination contributes to the podocytes injury in diabetic nephropathy.

The ubiquitination function in diabetic nephropathy (DN) has attracted much attention, but there is a lack of information on its ubiquitylome profile. To examine the differences in protein content and ubiquitination in the kidney between db/db mice and db/m mice, we deployed liquid chromatography-mass spectrometry (LC-MS/MS) to conduct analysis. We determined 145 sites in 86 upregulated modified proteins and 66 sites in 49 downregulated modified proteins at the ubiquitinated level. Moreover, 347 sites among the 319 modified proteins were present only in the db/db mouse kidneys, while 213 sites among the 199 modified proteins were present only in the db/m mouse kidneys. The subcellular localization study indicated that the cytoplasm had the highest proportion of ubiquitinated proteins (31.87%), followed by the nucleus (30.24%) and the plasma membrane (20.33%). The enrichment analysis revealed that the ubiquitinated proteins are mostly linked to tight junctions, oxidative phosphorylation, and thermogenesis. Podocin, as a typical protein of slit diaphragm, whose loss is a crucial cause of proteinuria in DN. Consistent with the results of ubiquitination omics, the K261R mutant of podocin induced the weakest ubiquitination compared with the K301R and K370R mutants. As an E3 ligase, c-Cbl binds to podocin, and the regulation of c-Cbl can impact the ubiquitination of podocin. In conclusion, in DN, podocin ubiquitination contributes to podocyte injury, and K261R is the most significant site. c-Cbl participates in podocin ubiquitination and may be a direct target for preserving the integrity of the slit diaphragm structure, hence reducing proteinuria in DN.

Adsorption of Cu (II) and Zn (II) in aqueous solution by modified bamboo charcoal.

Due to the development of industries such as mining, smelting, industrial electroplating, tanning, and mechanical manufacturing, heavy metals were discharged into water bodies seriously affecting water quality. Bamboo charcoal, as an environmentally friendly new adsorbent material, in this paper, the virgin bamboo charcoal (denoted as WBC) was modified with different concentrations of KMnO4 and NaOH to obtain KMnO4-modified bamboo charcoal (KBC) and NaOH-modified bamboo charcoal (NBC) which was used to disposed of water bodies containing Cu2+ and Zn2+. The main conclusions were as following: The adsorption of Cu2+ by WBC, KBC and NBC was significantly affected by pH value, and the optimum pH was 5.0. Differently, the acidity and alkalinity of the solution doesn't effect the adsorption of Zn2+ seriousely. Meanwhile, surface diffusion and pore diffusion jointly determine the adsorption rate of Cu2+ and Zn2+. The test result of EDS showed that Mn-O groups formed on the surface of K6 (WBC treated by 0.06 mol/L KMnO4) can promote the adsorption of Cu2+ and Zn2+ at a great degree. The O content on N6(WBC treated by 6 mol/L NaOH) surface increased by 30.95% compared with WBC. It is speculated that the increase of carbonyl group on the surface of NBC is one of the reasons for the improvement of Cu2+ and Zn2+ adsorption capacity. Finally, the residual concentrations of Cu2+ and Zn2+ in wastewater are much lower than 0.5 mg/L and 1.0 mg/L, respectively. Thus it can be seen, KBC and NBC could be a promising adsorbent for heavy metals.

Microplastics' toxic effects and influencing factors on microorganisms in biological wastewater treatment units.

Prior to entering the water body, microplastics (MPs) are mostly collected at the sewage treatment plant and the biological treatment unit is the sewage treatment facility's central processing unit. This review aims to present a comprehensive analysis of the detrimental impacts of MPs on the biological treatment unit of a sewage treatment plant and it covers how MPs harm the effluent quality of biological treatment processes. The structure of microbial communities is altered by MPs presence and additive release, which reduces functional microbial activity. Extracellular polymers, oxidative stress, and enzyme activity are explored as micro views on the harmful mechanism of MPs on microorganisms, examining the toxicity of additives released by MPs and the harm caused to microorganisms by harmful compounds that have been adsorbed in the aqueous environment. This article offers a theoretical framework for a thorough understanding of the potential problems posed by MPs in sewage treatment plants and suggests countermeasures to mitigate those risks to the aquatic environment.

Color construction of multi-colored carbon fibers using glucose.

Carbon fibers (CFs) have attracted attention in the automotive, aviation, and aerospace industries. However, the coloration of CFs is challenging due to their brittleness, inertness, complexity, and time/energy-intensive processes. Herein, inspired by the naturally grown protrusive nanostructures on the green central surface of peacock back feathers, we report an in-situ self-growing strategy for developing carbon spheres (CSs) on the CFs surface to achieve color tuning. This is achieved via the dynamic growth of CSs using glucose as the feeding material. Combined with the coloration process, the interaction between CSs and CFs promotes stable interfacial forces in integrated molding. This strategy allows the coloring system to continuously vary its color in a designated manner, thereby, endowing it with satisfactory mechanical robustness, acid durability, and light fastness. We anticipate this developed approach can be potentially competitive in the color construction of CFs with multi-colors due to its low-cost manufacturing.

Fractionated lignin as a green compatibilizer to improve the compatibility of poly (butylene adipate-co-terephthalate) /polylactic acid composites.

Blending poly (butylene adipate-co-terephthalate) (PBAT) and polylactic acid (PLA) is a cost-effective strategy to obtain biodegradable plastic with complementary properties. However, the incompatibility between PBAT and PLA is a great challenge for fabricating high-performance composite films. Herein, the ethyl acetate fractionated lignin with the small glass transition temperature and low molecular weight was achieved and incorporated into the PBAT/PLA composite as a compatibilizer. The fractionated lignin can be uniformly dispersed within the PBAT/PLA matrix through a melt blending process and interact with the molecular chain of PBAT and PLA as a bonding bridge, which enhances the intermolecular interactions and reduces the interfacial tension of PBAT/PLA. By adding fractionated lignin, the tensile strength of the PBAT/PLA composite increased by 35.4 % and the yield strength increased by 37.7 %. Owing to lignin, the composite films possessed the ultraviolet shielding function and exhibited better water vapor barrier properties (1.73 ± 0.08 × 10-13 g·cm/cm2·s·Pa). This work conclusively demonstrated that fractionated lignin can be used as a green compatibilizer and a low-cost functional filler for PBAT/PLA materials, and provides guidance for the application of lignin in biodegradable plastics.

The intervention of cannabinoid receptor in chronic and acute kidney disease animal models: a systematic review and meta-analysis.

AIM: Cannabinoid receptors are components of the endocannabinoid system that affect various physiological functions. We aim to investigate the effect of cannabinoid receptor modulation on kidney disease. METHODS: PubMed, Web of Science databases, and EMBASE were searched. Articles selection, data extraction and quality assessment were independently performed by two investigators. The SYRCLE's RoB tool was used to assess the risk of study bias, and pooled SMD using a random-effect model and 95% CIs were calculated. Subgroup analyses were conducted in preselected subgroups, and publication bias was evaluated. We compared the effects of CB1 and CB2 antagonists and/or knockout and agonists and/or genetic regulation on renal function, blood glucose levels, body weight, and pathological damage-related indicators in different models of chronic and acute kidney injury. RESULTS: The blockade or knockout of CB1 could significantly reduce blood urea nitrogen [SMD,- 1.67 (95% CI - 2.27 to - 1.07)], serum creatinine [SMD, - 1.88 (95% CI - 2.91 to - 0.85)], and albuminuria [SMD, - 1.60 (95% CI - 2.16 to - 1.04)] in renal dysfunction animals compared with the control group. The activation of CB2 group could significantly reduce serum creatinine [SMD, - 0.97 (95% CI - 1.83 to - 0.11)] and albuminuria [SMD, - 2.43 (95% CI - 4.63 to - 0.23)] in renal dysfunction animals compared with the control group. CONCLUSIONS: The results suggest that targeting cannabinoid receptors, particularly CB1 antagonists and CB2 agonists, can improve kidney function and reduce inflammatory responses, exerting a renal protective effect and maintaining therapeutic potential in various types of kidney disease.

Development of high internal phase Pickering emulsions stabilized by egg yolk and carboxymethylcellulose complexes to improve ß-carotene bioaccessibility for the elderly.

The work aimed to develop the multi-protein mixture of egg yolk as natural particles to stabilize high internal phase Pickering emulsions (HIPPEs) to improve the bioaccessibility of ß-carotene in the elderly. The results showed that the depletion attraction drove the adsorption of egg yolk protein particles at the oil-water interface and the formation of osmotic droplet clusters due to the attachment of particle-coated droplets in the dispersed phase, leading to kinetic blocking and stable gelation of HIPPEs. Rheological measurements showed that HIPPEs had shear thinning, low shear stress, viscoelastic properties, and structural recovery properties, which facilitated easy consumption for the elderly. The stability of HIPPEs was verified by ionic and centrifugal stability tests, demonstrating their potential for application to complex gastric environments. HIPPEs have been applied to the International Dysphagia Dietary Standardization Initiative (IDDSI) test and simulated in vitro digestion in older adults, demonstrating their safe swallowability and high ß-carotene bioaccessibility. Our findings suggest solutions for food practitioners facing the aging problem and provide new insights for preparing age-friendly foods.

Enhanced mechanic properties of calcium phosphate cements via mussel-inspired adhesive as bone substitute: Highlights of their interactions.

BACKGROUND: Inspired by natural bones, many organic components were added to Calcium Phosphate Cements (CPCs) to improve their mechanical strength. However, the strength of these composite CPCs is limited by the low strength of organic components itself and the weak interaction between organic components and CPCs. OBJECTIVE: Firstly, a composite CPC containing mussel-inspired adhesive, Poly-(Dopamine Methacrylamide-co-2-methoxy Ethylacrylate) (pDM) was developed. Secondly, the interactions between pDM and CPC and their effect on mechanical properties were investigated. METHODS: The interactions between pDM and CPC were performed by Nuclear Magnetic Resonance, Laser Raman, X-ray Photoelectron Spectroscopy, Fourier Transform-Infrared Spectroscopy and X-ray Diffraction Analysis. RESULTS: The toughness and compressive strength of pDM-CPC scaffold were both significantly enhanced, because of the enhanced interface binding strength among CPC and pDM due to their interaction and the improved mechanical strength of pDM owing to its self-oxidation cross-linking. The toughness of pDM-CPC scaffolds increased with the increased contents of pDM, while pDM-CPC scaffold containing 35 wt.% pDM had the highest compressive strength of all, which the latter was more than five times compared to that of CPC. CONCLUSION: The mechanically strong pDM-CPC scaffolds has potential application in bone regeneration as well as in craniofacial and orthopedic repair.

Effect of the substitution of butter by double cross-linked egg yolk granules/sodium alginate emulsion gel on properties of baking dough during frozen storage.

In this study, double cross-linked egg yolk granules (EYGs)/sodium alginate (SA) emulsion gel was constructed and used as butter substitute. The water binding capacity, rheology properties and microstructure of EYGs/SA emulsion gel showed that the network structure tended to be complete when the concentration of SA reached 1% (m/v). SA stabilized the EYGs/SA droplets and enhanced the spatial network structure of emulsion gel. After substitution for butter, the network structure of EYGs/SA emulsion gel with more water bounded and the polyhydroxy structure of SA molecules endowed dough with more water retention capacity. Meanwhile, the destruction of the microstructure of the replaced dough with EYGs/SA emulsion gel was significantly inhibited compared with the un-substituted dough after freezing. The baking ability results showed a satisfactory baking effect after substitution. Overall, this study provides a new avenue in the field of fat replacement and the application of EYGs/SA emulsion gels.

Predictors of futile recanalization after endovascular treatment in acute ischemic stroke: a multi-center study.

Background and objectives: Endovascular thrombectomy (EVT) improves long-term outcomes and decreases mortality in ischemic stroke patients. However, a significant proportion of patients do not benefit from EVT recanalization, a phenomenon known as futile recanalization or reperfusion without functional independence (RFI). In this study, we aim to identify the major stroke risk factors and patient characteristics associated with RFI. Methods: This is a retrospective cohort study of 297 consecutive patients with ischemic stroke who received EVT at three academic stroke centers in China from March 2019 to March 2022. Patient age, sex, modified Rankin Scale (mRS), National Institute of Health Stroke Scale (NIHSS), Alberta stroke program early CT score (ASPECTS), time to treatment, risk factors and comorbidities associated with cerebrovascular diseases were collected, and potential associations with futile recanalization were assessed. RFI was successful reperfusion defined as modified thrombolysis in cerebral infarction (mTICI) ≥ 2b without functional independence at 90 days (mRS ≥ 3). Results: Of the 297 initial patients assessed, 231 were included in the final analyses after the application of the inclusion and exclusion criteria. Patients were divided by those who had RFI (n = 124) versus no RFI (n = 107). Older age (OR 1.041, 95% CI 1.004 to 1.073; p = 0.010), chronic kidney disease (OR 4.399, 0.904-21.412; p = 0.067), and higher 24-h NIHSS (OR 1.284, 1.201-1.373; p < 0.001) were independent predictors of RFI. Conversely, an mTICI score of 3 was associated with a reduced likelihood of RFI (OR 0.402, 0.178-0.909; p = 0.029). Conclusion: In conclusion, increased age, higher 24-h NIHSS and lack of an mTICI score of 3 were independently associated with RFI and have potential prognostic values in predicting patients that are less likely to respond to EVT recanalization therapy.

Post-ASPECTS and Post-PC-ASPECTS Predict the Outcome of Anterior and Posterior Ischemic Stroke Following Thrombectomy.

Purpose: In this study, we aimed to determine whether post-Alberta Stroke Project Early CT Changes Score (post-ASPECTS) in anterior stroke and post-(posterior circulation) PC-ASPECTS in posterior stroke on CT can predict post-endovascular thrombectomy (EVT) functional outcomes among patients with acute ischemic stroke (AIS) after EVT. Patients and Methods: A total of 247 consecutive patients aged 18 and over receiving EVT for LVO-related AIS were recruited into a prospective database. The data was retrospectively analyzed between March 2019 and February 2022 from two comprehensive tertiary care stroke centers: Foshan Sanshui District People's Hospital and First People's Hospital of Foshan in China. Patient parameters included EVT within 24 hr of symptom onset, premorbid modified Rankin scale (mRS) ≤2, presence of distal and terminal cerebral blood vessel occlusion, and subsequent 24-72-hr post-stroke onset CT scan. Univariate comparisons were performed using the Fisher's exact test or χ2 test for categorical variables and the Mann-Whitney U-test for continuous variables. Logistic regression analysis was performed to further analyze for adjusting for confounding factors. A p-value of ≤0.05 was statistically significant. Results: Overall, 236 individuals with 196 anterior circulation ischemic strokes and 40 posterior strokes of basilar artery occlusion were examined. Post-ASPECTS in anterior stroke and post-pc-ASPECTS as strong positive markers of favorable outcome at 90 days post-EVT; and lower rates of inpatient mortality/hospice discharge, 90-day mortality, and 90-day poor outcome were observed. Moreover, patients in the post-ASPECTS ≥ 7 cohort experienced shorter door-to-recanalization time (DRT), puncture-to-recanalization time (PRT), and last known normal-to-puncture time (LKNPT). Conclusion: Post-ASPECTS ≥7 in anterior circulation AIS and post-pc-ASPECTS ≥7 in posterior circulation can serve as strong prognostic markers of functional outcome after EVT.

7-Day National Institutes of Health Stroke Scale as a surrogate marker predicting ischemic stroke patients' outcome following endovascular therapy.

Background: Early neurological deterioration after endovascular thrombectomy (EVT) is associated with poor prognosis. National Institutes of Health Stroke Scale (NIHSS) score measured at 24 h after EVT may be a better outcome predictor than other methods that focus on changes in NIHSS. Nevertheless, clinical fluctuations in ischemic stroke patients during the immediate phase after symptoms onset are well recognized. Therefore, a delayed NIHSS evaluation may improve prognostic accuracy. We evaluate the 7-day NIHSS in predicting long-term patient outcomes after EVT. Methods: This was a multi-center retrospective cohort study of 300 consecutive ischemic stroke patients with large vessel occlusion who underwent EVT at three-stroke centers in China from August 2018 to March 2022. NIHSS was recorded on admission, pre-EVT, 24 h, and 7 days after EVT. Results: A total of 236 eligible patients were subdivided into two groups: 7-day NIHSS ≤6 and NIHSS >6 post-EVT. 88.29% achieved a favorable outcome (modified Rankin Scale 0-2) in the NIHSS ≤6 group compared to 15.20% in the NIHSS >6 group at 90 days, and an improved favorable outcome in the former group was observed after adjusting for potential confounding factors (adjusted odds ratio 39.7, 95% confidence interval, 17.5-89.7, p < 0.001). Conclusion: The 7-day NIHSS score may be a reliable predictor of 90-day stroke patient outcome after EVT.

Predictors of failure of early neurological improvement in early time window following endovascular thrombectomy: a multi-center study.

Background and objective: Endovascular thrombectomy (EVT) has become the gold standard in the treatment of acute stroke patients. However, not all patients respond well to this treatment despite successful attempts. In this study, we aimed to identify variables associated with the failure of improvements following EVT. Methods: We retrospectively analyzed prospectively collected data of 292 ischemic stroke patients with large vessel occlusion who underwent EVT at three academic stroke centers in China from January 2019 to February 2022. All patients were above 18 years old and had symptoms onset ≤6 h. A decrease of more than 4 points on the National Institute of Health Stroke Scale (NIHSS) after 24 h compared with admission or an NIHSS of 0 or 1 after 24 h was defined as early neurological improvement (ENI), whereas a lack of such improvement in the NIHSS was defined as a failure of early neurological improvement (FENI). A favorable outcome was defined as a modified Rankin scale (mRS) score of 0-2 after 90 days. Results: A total of 183 patients were included in the final analyses, 126 of whom had FENI, while 57 had ENI. Favorable outcomes occurred in 80.7% of patients in the ENI group, in contrast to only 22.2% in the FENI group (p < 0.001). Mortality was 7.0% in the ENI group in comparison to 42.1% in the FENI group (p < 0.001). The multiple logistic regression model showed that diabetes mellitus [OR (95% CI), 2.985 (1.070-8.324), p = 0.037], pre-stroke mRS [OR (95% CI), 6.221 (1.421-27.248), p = 0.015], last known well to puncture time [OR (95% CI), 1.010 (1.003-1.016), p = 0.002], modified thrombolysis in cerebral infarction = 3 [OR (95% CI), 0.291 (0.122-0.692), p = 0.005], and number of mechanical thrombectomy passes [OR (95% CI), 1.582 (1.087-2.302), p = 0.017] were the predictors of FENI. Conclusion: Diabetes mellitus history, pre-stroke mRS, longer last known well-to-puncture time, lack of modified thrombolysis in cerebral infarction = 3, and the number of mechanical thrombectomy passes are the predictors of FENI. Future large-scale studies are required to validate these findings.

Analysis of potential biomarkers for diabetic kidney disease based on single-cell RNA-sequencing integrated with a single-cell sequencing assay for transposase-accessible chromatin.

Diabetic kidney disease (DKD) is a renal microvascular disease caused by hyperglycemia that involves metabolic remodeling, oxidative stress, inflammation, and other factors. The mechanism is complex and not fully unraveled. We performed an integrated single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) and single-cell RNA-sequencing (scRNA-seq) analyses of kidneys from db/db and db/m mice to identify differential open chromatin regions and gene expression, particularly in genes related to proximal tubular reabsorption and secretion. We identified 9,776 differentially expressed genes (DEGs) and 884 cell type-specific transcription factors (TFs) across 15 cell types. Glucose and lipid transporters, and TFs related to the circadian rhythm in the proximal tubules had significantly higher expression in db/db mice than in db/m mice (P<0.01). Crosstalk between podocytes and tubular cells in the proximal tubules was enhanced, and renal inflammation, oxidative stress, and fibrosis pathways were activated in db/db mice. Western blotting and immunohistochemical staining results showed that Wfdc2 expression in the urine and kidneys of DKD patients was higher than that in non-diabetic kidney disease (NDKD) controls. The revealed landscape of chromatin accessibility and transcriptional profiles in db/db mice provide insights into the pathological mechanism of DKD.

Identification of urinary extracellular vesicles differentially expressed RNAs in diabetic nephropathy via whole-transcriptome integrated analysis.

BACKGROUND: Diabetic nephropathy (DN) is a common systemic microvascular complication of diabetes and a leading cause of chronic kidney disease worldwide. Urinary extracellular vesicles (uEVs), which are natural nanoscale vesicles that protect RNA from degradation, have the potential to serve as an invasive diagnostic biomarker for DN. METHODS: We enrolled 24 participants, including twelve with renal biopsy-proven T2DN and twelve with T2DM, and isolated uEVs using ultracentrifugation. We performed microarrays for mRNAs, lncRNAs, and circRNAs in parallel, and Next-Generation Sequencing for miRNAs. Differentially expressed RNAs (DE-RNAs) were subjected to CIBERSORTx, ssGSEA analysis, GO enrichment, PPI network analysis, and construction of the lncRNA/circRNA-miRNA-mRNA regulatory network. Candidate genes and potential biomarker RNAs were validated using databases and machine learning models. RESULTS: A total of 1684 mRNAs, 126 lncRNAs, 123 circRNAs and 66 miRNAs were found in uEVs in T2DN samples compared with T2DM. CIBERSORTx revealed the involvement of uEVs in immune activity and ssGSEA explored possible cell or tissue sources of uEVs. A ceRNA co-expression and regulation relationship network was constructed. Candidate genes MYO1C and SP100 mRNA were confirmed to be expressed in the kidney using Nephroseq database, scRNA-seq dataset, and Human Protein Atlas database. We further selected 2 circRNAs, 2 miRNAs, and 2 lncRNAs from WGCNAs and ceRNAs and demonstrated their efficacy as potential diagnostic biomarkers for T2DN using machine learning algorithms. CONCLUSIONS: This study reported, for the first time, the whole-transcriptome genetic resources found in urine extracellular vesicles of T2DN patients. The results provide additional support for the possible interactions, and regulators between RNAs from uEVs themselves and as potential biomarkers in DN.