Rhodium nanozyme mitigates RPE degeneration and preserves vision in age-related macular degeneration via antioxidant and anti-inflammatory mechanisms.

Age-related macular degeneration (AMD) is the leading cause of blindness among elderly people worldwide. However, there are currently no effective treatments for AMD. Oxidative stress-induced retinal pigment epithelium (RPE) degeneration and the inflammatory response are the main causes of AMD. In this study, a polyethylene glycol (PEG)-coated rhodium nanozyme (PEG-RhZ) with excellent reactive oxygen species (ROS) and reactive nitrogen species (RNS) elimination capability was synthesized for the treatment of AMD. PEG-RhZs protected RPE cell viability and barrier function upon exposure to oxidative stress stimuli. Additionally, microglial migration and iNOS, IL-1ß and TNF-α expression were inhibited by PEG-RhZs. In the acute phase of the AMD model, PEG-RhZs significantly alleviated RPE oxidative damage and inhibited microglial activation. In the late stage of the AMD model, PEG-RhZs reduced photoreceptor loss and improved vision impairment. Furthermore, PEG-RhZs showed good biocompatibility and stability both in vitro and in vivo. Collectively, our findings suggest the therapeutic potential of PEG-RhZs for AMD treatment. STATEMENT OF SIGNIFICANCE: AMD is a kind of retinal degenerative disease that poses heavy health burden globally. PEG-RhZs exhibiting robust ROS and RNS scavenging capabilities have shown promise in safeguarding retinal pigment epithelium (RPE) from oxidative stress, suppressing microglia activation and the secretion of pro-inflammatory molecules, mitigating loss of retinal photoreceptor cells, and ameliorating visual impairment. The commendable antioxidant properties, biological safety, and biostability of PEG-RhZs offer valuable insights for the clinical management of AMD.

Targeting ferroptosis opens new avenues in gliomas.

Gliomas are one of the most challenging tumors to treat due to their malignant phenotype, brain parenchymal infiltration, intratumoral heterogeneity, and immunosuppressive microenvironment, resulting in a high recurrence rate and dismal five-year survival rate. The current standard therapies, including maximum tumor resection, chemotherapy with temozolomide, and radiotherapy, have exhibited limited efficacy, which is caused partially by the resistance of tumor cell death. Recent studies have revealed that ferroptosis, a newly defined programmed cell death (PCD), plays a crucial role in the occurrence and progression of gliomas and significantly affects the efficacy of various treatments, representing a promising therapeutic strategy. In this review, we provide a comprehensive overview of the latest progress in ferroptosis, its involvement and regulation in the pathophysiological process of gliomas, various treatment hotspots, the existing obstacles, and future directions worth investigating. Our review sheds light on providing novel insights into manipulating ferroptosis to provide potential targets and strategies of glioma treatment.

High-Quality Single Crystalline Sc0.37Al0.63N Thin Films Enabled by Precise Tuning of III/N Atomic Flux Ratio during Molecular Beam Epitaxy.

We attained wurtzite ScxAl1-xN (0.16 ≤ x ≤ 0.37) thin films by varying the Sc and Al fluxes at a fixed active nitrogen flux during plasma-assisted molecular beam epitaxy. Atomic fluxes of Sc and Al sources via measured Sc percentage in as-grown ScxAl1-xN thin films were derived as the feedback for precise determination of the ScxAl1-xN growth diagram. We identified an optimal III/N atomic flux ratio of 0.78 for smooth Sc0.18Al0.82N thin films. Further increasing the III/N ratio led to phase separation under N-rich conditions, validated by the observation of high-Sc-content hillocks with energy-dispersive X-ray spectroscopy mapping. At the fixed III/N ratio of 0.78, we found that phase separation with high-Al-content hillocks occurs for x > 0.37, which is substantially lower than the thermodynamically dictated threshold Sc content of ~0.55 in wurtzite ScxAl1-xN. We postulate that these wurtzite-phase purity degradation scenarios are correlated with adatom diffusion and the competitive incorporation process of Sc and Al. Therefore, the ScxAl1-xN growth window is severely restricted by the adatom kinetics. We obtained single crystalline Sc0.37Al0.63N thin films with X-ray diffraction (002)/(102) ω rocking curve full-width at half-maximums of 2156 arcsec and 209 arcsec and surface roughness of 1.70 nm. Piezoelectric force microscopy probing of the Sc0.37Al0.63N epilayer validates unambiguous polarization flipping by 180°.

Construction and validation of a TAMRGs prognostic signature for gliomas by integrated analysis of scRNA and bulk RNA sequencing data.

BACKGROUND: This study aimed to construct and validate a prognostic model based on tumor associated macrophage-related genes (TAMRGs) by integrating single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) data. METHODS: The scRNA-seq data of three inhouse glioma tissues were used to identify the tumor-associated macrophages (TAMs) marker genes, the DEGs from the The Cancer Genome Atlas (TCGA) - Genotype-Tissue Expression (GTEx) dataset were used to further select TAMs marker genes. Subsequently, a TAMRG-score was constructed by Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis in the TCGA dataset and validated in the Chinese Glioma Genome Atlas (CGGA) dataset. RESULTS: We identified 186 TAMs marker genes, and a total of 6 optimal prognostic genes including CKS2, LITAF, CTSB, TWISTNB, PPIF and G0S2 were selected to construct a TAMRG-score. The high TAMRG-score was significantly associated with worse prognosis (log-rank test, P<0.001). Moreover, the TAMRG-score outperformed the other three models with AUC of 0.808. Immune cell infiltration, TME scores, immune checkpoints, TMB and drug susceptibility were significantly different between TAMRG-score groups. In addition, a nomogram were constructed by combing the TAMRG-score and clinical information (Age, Grade, IDH mutation and 1p19q codeletion) to predict the survival of glioma patients with AUC of 0.909 for 1-year survival. CONCLUSION: The high TAMRG-score group was associated with a poor prognosis. A nomogram by incorporating TMARG-score could precisely predict glioma survival, and provide evidence for personalized treatment of glioma.

ProNGF elicits retrograde axonal degeneration of basal forebrain neurons through p75NTR and induction of amyloid precursor protein.

Basal forebrain cholinergic neurons (BFCNs) extend long projections to multiple regions in the brain to regulate cognitive functions. Degeneration of BFCNs is seen with aging, after brain injury, and in neurodegenerative disorders. An increase in the amount of the immature proform of nerve growth factor (proNGF) in the cerebral cortex results in retrograde degeneration of BFCNs through activation of proNGF receptor p75NTR. Here, we investigated the signaling cascades initiated at the axon terminal that mediate proNGF-induced retrograde degeneration. We found that local axonal protein synthesis and retrograde transport mediated proNGF-induced degeneration initiated from the axon terminal. Analysis of the nascent axonal proteome revealed that proNGF stimulation of axonal terminals triggered the synthesis of numerous proteins within the axon, and pathway analysis showed that amyloid precursor protein (APP) was a key upstream regulator in cultured BFCNs and in mice. Our findings reveal a functional role for APP in mediating BFCN axonal degeneration and cell death induced by proNGF.

Efficient Solid-Phase Extraction of Neonicotinoid Insecticides from Environmental Water and Drink Samples Using a Postmodified Metal-Organic Framework.

Neonicotinoid insecticides (NNIs) are extensively utilized globally because of their efficient and broad-spectrum properties. However, their residues are also extensively distributed in the environment. Herein, MIL-101-SO3Na with abundant -NH- and sulfonate groups was synthesized via chloromethylation and nucleophilic substitution postmodification strategies and used to extract NNIs via solid-phase extraction. MIL-101-SO3Na was enhanced by introducing C-H···N hydrogen bonds to strengthen interaction forces and -SO3Na groups to adjust surface charge and enhance electrostatic attraction. This modification and the substantial specific surface area (998 m2·g-1) of the metal-organic framework markedly enhanced the enrichment efficiency of MIL-101. The proposed method based on MIL-101-SO3Na exhibited a minimal detection threshold (0.04-0.87 ng·L-1), an extensive linear spectrum (1-2000 ng·L-1), and notable accuracy (a variation of 3.02-11.8%) in water and drink samples. NNI concentrations between 0.25 and 24.2 ng·L-1 in fruit juice and tea samples were accurately identified using the proposed method, demonstrating its feasibility in practical applications. The postmodification of MIL-101-SO3Na is an exceptional and promising approach for the sensitive detection of ultratrace NNI levels in complex matrices.

Unraveling the fate of 6PPD-Q in aquatic environment: Insights into formation, dissipation, and transformation under natural conditions.

The widespread occurrence of N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) in aquatic environments and its hazards to aquatic species underscore the necessity of comprehending its environmental fate. Here, we investigated the transformation from 6PPD to 6PPD-Q and the attenuation of 6PPD-Q in surface water under natural conditions. Contrary to prior findings, this work revealed that 6PPD-Q and its precursor 6PPD-OH/6PPD-(OH)2, were not detected through target analysis and suspect screening during 6PPD transformation in the surface water under the natural conditions. 6PPD-Q predominantly accumulated in TWPs in ambient atmosphere with 1.28 % mass yield from the 6PPD dissipation. Subsequently, 6PPD-Q was eluted from TWPs and released to the water environment. The investigation on the natural attenuation of 6PPD-Q in the surface water demonstrated that direct and indirect photolysis facilitated the rapid dissipation of 6PPD-Q with a half-life of 2.57 h. Utilizing the liquid chromatography high resolution mass spectrometry (LC-HRMS), including both time of flight (TOF) MS and Orbitrap MS, twelve novel transformation products (TPs) of 6PPD-Q were identified by using a comprehensive non-targeted screening strategy. The results from two dimensions gas chromatography (GC×GC) TOF-MS revealed additional two TPs. Based on the molecular structure of TPs, four major pathways of 6PPD-Q attenuation were proposed, including bond cleavage, hydroxylation, quinone cleavage and rearrangement. All TPs were predicted to exhibit lower toxicity, indicating the natural attenuation of 6PPD-Q reduced its toxicity and potential environmental risks. This study provides crucial insights into the environmental fate of 6PPD-Q, highlighting the significance of understanding both its formation from 6PPD and its subsequent attenuation processes under natural conditions.

A Bayesian inference model can predict the effects of attention on the serial dependence in heading estimation from optic flow.

It has been demonstrated that observers can accurately estimate their self-motion direction (i.e., heading) from optic flow, which can be affected by attention. However, it remains unclear how attention affects the serial dependence in the estimation. In the current study, participants conducted two experiments. The results showed that the estimation accuracy decreased when attentional resources allocated to the heading estimation task were reduced. Additionally, the estimates of currently presented headings were biased toward the headings of previously seen headings, showing serial dependence. Especially, this effect decreased (increased) when the attentional resources allocated to the previously (currently) seen headings were reduced. Furthermore, importantly, we developed a Bayesian inference model, which incorporated attention-modulated likelihoods and qualitatively predicted changes in the estimation accuracy and serial dependence. In summary, the current study shows that attention affects the serial dependence in heading estimation from optic flow and reveals the Bayesian computational mechanism behind the heading estimation.

Covalent Organic Framework Membranes with Regulated Orientation for Monovalent Cation Sieving.

Continuous covalent organic framework (COF) thin membranes have garnered broad concern over the past few years due to their merits of low energy requirements, operational simplicity, ecofriendliness, and high separation efficiency in the application process. This study marks the first instance of fabricating two distinct, self-supporting COF membranes from identical building blocks through solvent modulation. Notably, the precision of the COF membrane's separation capabilities is substantially enhanced by altering the pore alignment from a random to a vertical orientation. Within these confined channels, the membrane with vertically aligned pores and micron-scale stacking thickness demonstrates rapid and selective transportation of Li+ ions over Na+ and K+ ions, achieving Li+/K+ and Li+/Na+ selectivity ratios of 38.7 and 7.2, respectively. This research not only reveals regulated orientation and layer stacking in COF membranes via strategic solvent selection but also offers a potent approach for developing membranes specialized in Li+ ion separation.

Reversible Schiff Base Chemistry in Arginine-Grafted Regenerated Cellulose Hydrogel: Integration of Chitosan and Zinc Ions for Enhanced Hemostasis, Antibacterial Action, and Accelerated Wound Healing.

Wound healing presents a formidable challenge for global healthcare systems. We aimed to address this challenge by designing a multifunctional wound dressing tailored to meet diverse therapeutic needs. Arginine (Arg), selected for its ability to promote wound healing, is grafted onto aldehyde-modified regenerated cellulose (DAC) via Schiff base bonds for a reversible controlled release. At the same time, DAC provides hemostatic function, while Zn2+ plays an antibacterial role and strengthens cross-linking within the dressing matrix. The hydrogels were characterized by FTIR, XRD, SEM, and EDS. Mechanical strength, adhesion, swelling, water retention, oxygen permeability, hemostasis, antioxidant capacity, and antibacterial activity were all rigorously evaluated to demonstrate the superior properties of the dressing, which promotes accelerated wound healing. The skin of injured mice has been shown to recover almost completely within 13 days of dressing treatment. These findings highlight the potential of this innovative multifunctional wound dressing to address complex wound management challenges.

Comprehensive analysis of GINS subunit expression, prognostic value, and immune infiltration in clear cell renal cell carcinoma.

Background: In recent decades, there has been increasing evidence that Go-Ichi-Nii-San (GINS) subunits play an important role in the development and progression of various tumors. However, little research has been conducted on the role of GINS subunits in clear cell renal cell carcinoma (ccRCC). This study sought to explore the differential expression, prognosis, and immunological significance of GINS subunits in ccRCC. Methods: We used various analysis packages of R (version 3.6.3), the University of ALabama at Birmingham CANcer (UALCAN) data analysis portal, the Cancer Cell Line Encyclopedia (CCLE), the cBio Cancer Genomics Portal (cBioPortal), and the Tumor Immune Estimation Resource (TIMER) to study the gene expression, promoter methylation level, gene mutations, prognostic and diagnostic value, immune infiltration, pathway enrichment, and other aspects of the GINS subunits. Next, the genes related to the GINS subunits were analyzed using the STRING and GeneMANIA platforms, and the correlation between GINS subunits and the functions involved were investigated. Results: The expression level of GINS1/2/3/4 was significantly higher in ccRCC tumor tissues than normal tissues, and was significantly related to tumor grade and stage. The expression of GINS1/2/4 may be related to the methylation degree of the promoter region. The prognostic and diagnostic analyses showed that the increased expression of GINS1 was associated with various poor prognoses and had diagnostic value. The GINS subunit mutation also significantly affected the clinical prognosis of ccRCC patients. Finally, the correlation analysis of the immune infiltration level, co-expression, and enrichment of related genes indicated that GINS subunit expression was associated with different levels of ccRCC immune infiltration. Conclusions: The analysis results showed that the differential expression of GINS subunits in ccRCC, which had prognostic and diagnostic value, was correlated with clinicopathological stage, immune infiltration, and other related aspects. GINS1 may serve as a new potential prognostic biomarker for ccRCC patients and be used to guide treatment.

Alterations in Astrocyte Subpopulations in Glioma and Identification of Cuproptosis-Related Genes Using Single-Cell RNA Sequencing.

Purpose: Mitochondrial metabolism is essential for energy production and the survival of brain cells, particularly in astrocytes. Cuproptosis is a newly identified form of programmed cell death that occurs due to the disruption of mitochondrial metabolism caused by excessive copper toxicity. However, the relationship between cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) and the prognosis of gliomas remains unclear. Patients and Methods: In this study, we utilized 32,293 cells obtained from three in-house single-cell RNA sequencing (scRNA-seq) datasets, along with 6,148 cells acquired from the Chinese Glioma Genome Atlas (CGGA) involving 14 glioma patients, to identify and validate the TME of gliomas. Results: Based on an analysis of 32,293 single cells, we investigated intra-tumor heterogeneity, intercellular communication, and astrocyte differentiation trajectories in gliomas. Our findings revealed that the TGFß signaling pathway exhibited a higher relative strength in astrocyte subpopulations. Additionally, we identified a novel three-gene signature (CDKN2A, SOX2, and MPC1) was identified for prognostic prediction. Furthermore, glioma patients with a high-risk score demonstrated poorer overall survival (OS) compared to those with a low-risk score in both training and testing datasets (P training set < 0.001; P test set = 0.037). Conclusion: Our study revealed the prognostic value of the CRGs in astrocytes exhibiting tumor immunosuppressive characteristics in glioma. We established a novel three-gene prognostic model that offers new insights into the prognosis and treatment strategies for gliomas.

Development and psychometric assessment of a health action process approach (HAPA) inventory for home nutritional behavior among postoperative gastric cancer patients.

Objective: The aim of this study was to develop and validate a health action process approach (HAPA) inventory for measuring cognitive belief factors influencing home nutritional behavior among postoperative gastric cancer patients. Methods: Item pool of the inventory was constructed based on the HAPA, literature review, and qualitative interview. Expert consultations were used for item improvement. Then postoperative gastric cancer patients (n = 404) were surveyed to conduct item analysis, reliability and validity test of the inventory. Reliability was evaluated through internal, split-half, and test-retest reliability. Validity was assessed through content and construct validity. Results: Starting with 44 items in the item pool, the final inventory comprised 23 items. The exploratory factor analysis identified six dimensions-namely, risk perception, outcome expectancy, self-efficacy, intention, action planning, coping planning. And the cumulative variance contribution rate was 70.676%. Confirmatory factor analysis showed the model fits well (χ2 = 370.794, df = 214, and χ2/df = 1.733, root mean square of approximation error = 0.054, comparative fit index = 0.943, Tucker-Lewis index = 0.933, and incremental fitting index = 0.944). The item and scale level content validity were 0.83-1.00, and 0.98, which was considered good. The reliability was acceptable (Cronbach's α = 0.922, split-half reliability = 0.781, test-retest reliability = 0.716). Conclusions: The developed inventory was valid and reliable to assess HAPA-based cognitive belief factors of home nutritional behavior of postoperative gastric cancer patients. Future research is needed to examine the applicability of the inventory in patients across diverse cultural backgrounds and healthcare systems.

Effects of wheat germ diet on intestinal antioxidant capacity, immunological function and gut microbiota of Sichuan white geese.

Background: Wheat germ is known for its antioxidant, anti-inflammatory, and disease resistance properties in animals. However, its effect on the gut of Sichuan white geese remains unclear. Method: In this study, thirty 250-day-old geese were divided into three equal groups, the control group, LWG group (21.8% wheat germ) and HWG group (43.6% wheat germ), the experiment lasted 12 weeks. We assessed various aspects of geese intestinal health, including barrier function, digestibility, antioxidant capacity, immunity, microbiota, and metabolism. Results: The study revealed a significant increase in villus height (VH), villus height-to-crypt depth (VH/CD) ratio, amylase, and lipase activities in the duodenum and ileum, increased putrescine levels in the duodenum and jejunum, as well as spermidine levels in the jejunum (P < 0.05). LWG increased the total antioxidant capacity (T-AOC) in the duodenum, while decreasing levels of intestinal malondialdehyde (MDA), serum lipopolysaccharide (LPS), interleukin-6 (IL-6), and diamine oxidase (DAO) activity (P < 0.05). Furthermore, LWG increased the relative abundance of Oscillospiraceae_unclassified, Ligilactobacillus, and Roseburia, as well as increased levels of acetic acid, butyric acid, and valeric acid, while decreasing the relative abundance of Subdoligranulum, Flavonifractor, and Klebsiella. Additionally, we observed 17 up-regulated genes and 25 down-regulated genes in the jejunum, which are associated with the cell cycle and immunity. These genes play roles in pathways such as the p53 signaling pathway, cell cycle regulation, and pathways associated with immune modulation. On the other hand, HWG increased intestinal VH and spermidine levels, as well as amylase and lipase activities in the duodenum (P < 0.05). It also elevated ileal T-AOC and sIgA levels (P < 0.05), while reducing intestinal MDA content, serum LPS levels, DAO activity, and propionic acid in cecum contents (P < 0.05). Moreover, HWG increased the relative abundance of Ligilactobacillus, Oscillospiraceae_unclassified, and Roseburia (P < 0.05). Conclusion: Overall, wheat germ diets, particularly the LWG diet demonstrated the ability to enhance antioxidant capacity, digestibility, immunity, and barrier properties of the intestinal tract, while modulating the gut microbiota and metabolism. Therefore, wheat germ diets hold promise in improving intestinal health by preserving barrier function and regulating flora structure.

pH-Sensitive and Redox-Responsive Poly(Tetraethylene Glycol) Nanoparticle-Based Platform for Cancer Treatment.

Effective drug delivery with precise tumour targeting is crucial for cancer treatment. To address the challenges posed by the specificity and complexity of the tumour microenvironment, we developed a poly(tetraethylene glycol)-based disulfide nanoparticle platform and explored its potential in cancer treatment, focusing on drug loading and controlled release performance. Poly(tetraethylene glycol) nanoparticles were characterised using nuclear magnetic resonance spectroscopy, mass spectrometry, and ultraviolet-visible spectroscopy. Additionally, we evaluated physicochemical properties, including dynamic light scattering, zeta potential analysis, drug loading capacity, and drug loading efficiency. The impact of nanoparticles on the mouse colorectal cancer cell line (CT26) and NIH3T3 cells was assessed using a cytotoxicity assay, live/dead staining assay, flow cytometry, and confocal fluorescence microscopy. The experimental results align with the expected chemical structure and physicochemical properties of poly(tetraethylene glycol) nanoparticles. These nanoparticles exhibit high drug loading efficiency (78.7%) and drug loading capacity (12%), with minimal changes in particle size over time in different media. In vitro experiments revealed that the nanoparticles can induce significant cytotoxicity and apoptosis in CT26 cells. Cellular uptake notably increases with increasing concentration and exposure time. The confocal microscopic analysis confirmed the effective distribution and accumulation of nanoparticles within cells. In conclusion, poly(tetraethylene glycol) nanoparticles hold promise for improving drug-delivery efficiency, offering potential advancements in cancer treatment.

Screening value of methylated Septin9 and lymphocyte-to-monocyte ratio in colorectal cancer.

The lymphocyte-to-monocyte ratio (LMR) is an indicator of inflammation in blood routine tests; however, little is known about its screening value in patients with colorectal cancer (CRC). The aim of this study was to explore the screening value of LMR and methylated Septin9 (mSEPT9) in CRC patients. The clinical data of 420 patients with CRC, 61 with adenomatous polyps, and 175 healthy individuals from 2018 to 2022 were retrospectively analyzed, and corresponding predictive nomograms were established. The results showed that the levels of LMR and mSEPT9 in the CRC group were significantly lower than those in the control group (P < .05). Meanwhile, the levels of LMR and mSEPT9 in right-sided CRC were significantly lower than those in left-sided CRC (P < .05). With the progression of CRC from stage I to IV, the levels of LMR and mSEPT9 also decreased gradually, and the levels of mSEPT9 in stages III and IV were significantly lower than those in stages I and II (P < .05). Receiver operating curve (ROC) results showed that mSEPT9 had the highest single diagnostic value for CRC, with an area under curve (AUC) of 0.810. The LMR with mSEPT9 combination showed the best combined diagnostic value for CRC, with AUC of 0.885. When the cutoff values of mSEPT9 and LMR were taken as 43.835 and 3.365, the sensitivity and specificity of this combination reached 82.3% and 84.6%, respectively. Our findings suggest that LMR and mSEPT9 differ in non-tumor group and CRC groups with different subtypes and stages, LMR with mSEPT9 combination can further improve sensitivity, and the novel predictive nomogram for CRC based on LMR and mSEPT9 can be further promoted.

Baicalin relieves complement alternative pathway activation-induced lung inflammation through inhibition of NF-κB pathway.

INTRODUCTION: Acute lung injury (ALI) as one kind of acute pulmonary inflammatory disorder, manifests primarily as damage to alveolar epithelial cells and microvascular endothelial cells. Activation of the complement system is a common pathological mechanism in ALI induced by diverse factors, with the complement alternative pathway assuming a pivotal role. Baicalin, a flavonoid derived from the root of Scutellaria baicalensis Georgi, exhibits noteworthy biological activities. The present study attempted the interventional effects and underlying mechanisms of baicalin in microangiopathy in ALI induced by complement alternative pathway activation. METHODS: Activation of the complement alternative pathway by cobra venom factor (CVF). HMEC cells were pretreated with baicalin and then exposed to complement activation products. The expression of inflammatory mediators was detected by ELISA, and the intranuclear transcriptional activity of NF-κB was assessed by a dual fluorescent kinase reporter gene assay kit. Before establishing the ALI mouse model, baicalin or PDTC was gavaged for 7 d. CVF was injected into the tail vein to establish the ALI model. The levels of inflammatory mediators in BALF and serum were determined by ELISA. HE staining and immunohistochemistry evaluated pathological changes, complement activation product deposition, and NF-κB p65 phosphorylation in lung tissue. RESULTS: Baicalin reduced complement alternative activation product-induced expression of HMEC cells adhesion molecules (ICAM-1, VCAM-1, E-selectin) and cytokines (IL-6, TNF-α) as well as upregulation of NF-κB intranuclear transcriptional activity. Baicalin intervention reduced the number of inflammatory cells and protein content in the BALF and decreased the levels of IL-6, TNF-α, and ICAM-1 in serum and IL-6, TNF-α, ICAM-1, and P-selectin in BLAF. In addition, baicalin attenuated inflammatory cell infiltration in the lung of ALI mice and reduced the deposition of complement activation products (C5a, C5b-9) and phosphorylation of NF-κB p65 in lung tissue. CONCLUSION: Baicalin relieves complement alternative pathway activation-induced lung inflammation by inhibition of NF-κB pathway, delaying the progression of ALI.

Biocompatible WSe2@BSA Dots with Merged Catalyst and Coreactant for Efficient Electrochemiluminescence.

Electrochemiluminescence (ECL) is a powerful tool for clinical diagnosis due to its exceptional sensitivity. However, the standard tripropylamine (TPrA) coreactant for Ru(bpy)3Cl2, the most widely studied and used ECL system, is highly toxic. Despite extensive research on alternative coreactants, they often fall short in poor efficiency. From a reaction kinetics perspective, accelerating electrooxidation rate of Ru(bpy)3Cl2 is an essential way to compensate the efficiency limitation of coreactants, but is rarely reported. Here, a hybrid electrocatalyst@coreactant dots for the ECL of Ru(bpy)3Cl2 is reported. The as-prepared WSe2@bovine serum albumin (WSe2@BSA) dots is biocompatible, and demonstrate dual functions, i.e., the BSA shell works as a coreactant, meanwhile, the WSe2 core effectively catalyzes Ru(bpy)3Cl2 oxidation. As a result, WSe2@BSA dots exhibit an exceptionally high efficiency comparable to TPrA for the ECL of Ru(bpy)3Cl2. In addition, the procedure for synthesizing WSe2@BSA dots is facile (room temperature, atmospheric conditions), rapid (5 min), and scalable (for millions of bioassays). A biosensor utilizing WSe2@BSA dots shows promise for highly sensitive detecting glypican-3 in clinical liver cancer serum samples, especially for alpha-fetoprotein-negative patients. This work opens a new avenue for developing a highly efficient ECL system for biosensing and clinical diagnosis.

Efficiency of HoLEP in patients with detrusor underactivity and renal dysfunction secondary to BPO.

PURPOSE: The purpose of this study was to assess the bladder and renal functional outcomes of holmium laser enucleation of the prostate (HoLEP) in patients with benign prostatic obstruction (BPO) complicated by detrusor underactivity (DU) and secondary renal dysfunction. METHODS: Thirty-one patients were included in this prospective study. Eligible patients had urinary retention, a bladder outlet obstruction index (BOOI) greater than 40, a bladder contractility index (BCI) less than 100, abnormal renal function at the initial diagnosis (serum creatinine > 132 µmol/L) and a renal pelvis anteroposterior diameter (PRAPD) > 1.5 cm bilaterally. All patients underwent HoLEP in a routine manner and were evaluated preoperatively and at 1, 3 and 6 months after surgery. The baseline characteristics of the patients, perioperative data, postoperative outcomes and complications were assessed. RESULTS: Significant improvement was observed in the international prostate symptom score (IPSS), quality of life (QoL) score, maximal urinary flow rate (Qmax), post-void residual volume (PVR), Scr and RPAPD at the 6-month follow-up. Bladder wall thickness (BWT) exhibited a decreasing trend but did not significantly differ from the preoperative values. No grade 3 or higher adverse events occurred, and grade 3 and lower complications were treated conservatively. Three patients required reinsertion of indwelling catheters, and they were able to void spontaneously after two weeks of catheterisation training and medication treatment. CONCLUSION: HoLEP is an effective treatment for men with BPO accompanied by DU and consequent renal function impairment. Patients are able to regain spontaneous voiding. Both bladder and renal functions were preserved and improved.