A new fluorescent probe with high selectivity and sensitivity for Cys detection in bovine serum.

Cysteine (Cys) is one of the most basic mercaptans in the human body. As an important endogenous small molecule mercaptan, Cys plays a vital role in various physiological processes and can participate in maintaining redox balance to ensure homeostasis. Abnormal Cys levels can lead to a variety of diseases. However, the detection of cysteine may be interfered with by other small molecule biothiols. Therefore, the design of fluorescent probes based on the structural characteristics and reactivity of cysteine has become the focus of current research. In this paper, a fluorescent probe (3-(2H-benzo[d][1,2,3]triazol-2-yl)-2-oxo-2H-benzo[g]chromen-8-yl acrylate, BTAB) for Cys detection was synthesized with acrylic ester as the reaction site. Under the conditions of gradual optimization, BTAB can achieve selectivity and anti-interference ability for Cys detection. The linear range of Cys was 0.3-10 µM, and the detection limit was 0.154 µM. Finally, this probe was applied to detect the Cys content in bovine serum samples with satisfactory results.

The relationship between ischemic penumbra progression and the oxygen content of cortex microcirculation in acute ischemic stroke.

The precise oxygen content thresholds of ischemic deep parenchymal (OCIDP) and that in cortical microcirculation (OCCM), which leads to ischemic penumbra converting into the infarcted core, remain uncertain. This study employed an invasive fiber-optic oxygen meter and a newly developed oxygen-responsive probe called RuA3-Cy5-rtPA (RC-rtPA) based on recombinant tissue-type plasminogen activator (rtPA) to examine the oxygen content thresholds. A mouse model of middle cerebral artery occlusion was generated and animals were randomly divided into a sham, 24-h reperfusion after 3-h ischemia (IR 3-h), and IR 6-h groups, all of which were sacrificed following reperfusion. Stroke severity was evaluated based on the infarction area, neurological symptoms, microcirculation perfusion, and microemboli in microcirculation. OCIDP was characterized based on its extent and distribution, whereas OCCM was measured using RC-rtPA. During ischemia, stroke severity escalation manifested as increasing infarction area, severe neurologic symptoms, and poorer microcirculation perfusion with more microthrombi depositions. OCIDP presented rapid decline following artery occlusion along with a gradual increase in the hypoxic area. Within 3 â€‹h following ischemia induction, the ischemic tissue that experienced hypoxia could be rescued, and this reversibility would disappear after 6 â€‹h. Within 6 â€‹h, OCCM continued to decrease. A significant decrease in oxygen content in cortical venules and cortical parenchyma was observed. These findings assist in establishing the extent of the ischemic penumbra at the microcirculation level and offer a foundation for assessing the ischemic penumbra that could respond positively to reperfusion therapy beyond the typical time window.

The calcium-dependent protein kinase CPK16 regulates hypoxia-induced ROS production by phosphorylating the NADPH oxidase RBOHD in Arabidopsis.

Reactive oxygen species (ROS) production is a key event in modulating plant responses to hypoxia and post-hypoxia reoxygenation. However, the molecular mechanism by which hypoxia-associated ROS homeostasis is controlled remains largely unknown. Here, we showed that the calcium-dependent protein kinase CPK16 regulates plant hypoxia tolerance by phosphorylating the plasma membrane-anchored NADPH oxidase RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD) to regulate ROS production in Arabidopsis (Arabidopsis thaliana). In response to hypoxia or reoxygenation, CPK16 was activated through phosphorylation of its Ser274 residue. The cpk16 knockout mutant displayed enhanced hypoxia tolerance, whereas CPK16-overexpressing (CPK16-OE) lines showed increased sensitivity to hypoxic stress. In agreement with these observations, hypoxia and reoxygenation both induced ROS accumulation in the rosettes of CPK16-OEs more strongly than in rosettes of the cpk16-1 mutant or the wild type. Moreover, CPK16 interacted with and phosphorylated the N terminus of RBOHD at four serine residues (Ser133, Ser148, Ser163, and Ser347) that were necessary for hypoxia- and reoxygenation-induced ROS accumulation. Furthermore, the hypoxia-tolerant phenotype of cpk16-1 was fully abolished in the cpk16 rbohd double mutant. Thus, we have uncovered a regulatory mechanism by which the CPK16-RBOHD module shapes ROS production during hypoxia and reoxygenation in Arabidopsis.

Circ_0081723 enhances cervical cancer progression and modulates CREBRF via sponging miR-545-3p.

Circular RNAs (circRNAs) have been confirmed to be an important modulator and therapeutic target of cervical cancer (CC). The aim of this study is to explore the role and mechanism of circ_0081723 in CC progression. Circ_0081723, microRNA-545-3p (miR-545-3p), and CREB3 regulatory factor (CREBRF) levels were detected using quantitative real-time PCR (qRT-PCR) assay. CREBRF, ki-67, Bcl-2 related X protein (Bax), and E-cadherin expression levels were determined using western blot (WB) and immunohistochemistry (IHC) assays. Cell proliferation was assessed using Cell Counting Kit-8 (CCK-8), cell colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assays. Flow cytometry was used to measure cell apoptosis.  Cell migration and invasion were examined using Transwell assay. Interaction between miR-545-3p and circ_0081723 or CREBRF was verified using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assays. The biological role of circ_0081723 on CC growth was examined using the xenograft tumor model in vivo. Circ_0081723 and CREBRF were increased, and miR-545-3p was decreased in CC tissues and cells. Circ_0081723 silencing suppressed CC cell growth and motility whereas boosted CC cell apoptosis. Besides, circ_0081723 acted as a molecular sponge for miR-545-3p, and circ_0081723 knockdown-induced effects were largely reversed by miR-545-3p downregulation in CC cells. Moreover, miR-545-3p repressed CC progression by targeting CREBRF.  Circ_0081723 absence blocked xenograft tumor growth in vivo. Circ_0081723 stimulated CC cell malignant behaviors by regulating the miR-545-3p/CREBRF pathway, providing a possible circRNA-targeted therapy for CC.

Maternal and neonatal outcomes and clinical laboratory testing of pregnant women with COVID-19 during the BA.5.2/BF.7 surge.

The impact of COVID-19 on pregnant women and newborns continues to be a critical societal concern. However, the majority of research focuses on the disease resulting from the early pandemic variants, without sufficient study on the more recent BA.5.2/BF.7. We retrospectively recruited pregnant women giving birth during the surge of the BA.5.2/BF.7 and analysed the risk impact of COVID-19 on maternal and neonatal outcomes. Furthermore, subjects matched through propensity scores were used for the analysis of clinical laboratory tests. A total of 818 pregnant women were enrolled, among 276 (33.7%) were diagnosed with SARS-CoV-2 during childbirth. COVID-19 significantly increased the risk of a hospital length of stay equal to or greater than seven days and neonatal admission to the neonatal intensive care unit, with an aHR of 2.03 (95% CI, 1.22-3.38) and 1.51 (95% CI, 1.12-2.03), respectively. In the analysis of 462 matched subjects, it was found that subjects infected with SARS-CoV-2 tended slight leucopenia and coagulation abnormalities. We found that during the surge of the BA.5.2/BF.7, COVID-19 increased the risk of maternal and neonatal outcomes among Chinese pregnant women. This finding offers significant insights to guide clinical practices involving pregnant women infected with the recently emerged Omicron subvariants.

DCAF1 interacts with PARD3 to promote hepatocellular carcinoma progression and metastasis by activating the Akt signaling pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is a fatal malignancy with poor prognosis due to lack of effective clinical interference. DCAF1 plays a vital role in regulating cell growth and proliferation, and is involved in the progression of various malignancies. However, the function of DCAF1 in HCC development and the underlying mechanism are still unknown. This study aimed to explore the effect of DCAF1 in HCC and the corresponding molecular mechanism. METHODS: Quantitative real-time PCR, Western blot and immunostaining were used to determine DCAF1 expression in tumor tissues and cell lines. Subsequently, in vitro and in vivo experiments were conducted to explore the function of DCAF1 in tumor growth and metastasis in HCC. Coimmunoprecipitation, mass spectrometry and RNA sequencing were performed to identify the underlying molecular mechanisms. RESULTS: In this study, we found that DCAF1 was observably upregulated and associated with poor prognosis in HCC. Knockdown of DCAF1 inhibited tumor proliferation and metastasis and promoted tumor apoptosis, whereas overexpressing DCAF1 yielded opposite effects. Mechanistically, DCAF1 could activate the Akt signaling pathway by binding to PARD3 and enhancing its expression. We also found that the combined application of DCAF1 knockdown and Akt inhibitor could significantly suppress subcutaneous xenograft tumor growth. CONCLUSIONS: Our study illustrates that DCAF1 plays a crucial role in HCC development and the DCAF1/PARD3/Akt axis presents a potentially effective therapeutic strategy for HCC.

Recent advances in microplastic removal from drinking water by coagulation: Removal mechanisms and influencing factors.

Microplastics (MPs) are emerging contaminants that are widely detected in drinking water and pose a potential risk to humans. Therefore, the MP removal from drinking water is a critical challenge. Recent studies have shown that MPs can be removed by coagulation. However, the coagulation removal of MPs from drinking water remains inadequately understood. Herein, the efficiency, mechanisms, and influencing factors of coagulation for removing MPs from drinking water are critically reviewed. First, the efficiency of MP removal by coagulation in drinking water treatment plants (DWTPs) and laboratories was comprehensively summarized, which indicated that coagulation plays an important role in MP removal from drinking water. The difference in removal effectiveness between the DWTPs and laboratory was mainly due to variations in treatment conditions and limitations of the detection techniques. Several dominant coagulation mechanisms for removing MPs and their research methods are thoroughly discussed. Charge neutralization is more relevant for small-sized MPs, whereas large-sized MPs are more dependent on adsorption bridging and sweeping. Furthermore, the factors influencing the efficiency of MP removal were jointly analyzed using meta-analysis and a random forest model. The meta-analysis was used to quantify the individual effects of each factor on coagulation removal efficiency by performing subgroup analysis. The random forest model quantified the relative importance of the influencing factors on removal efficiency, the results of which were ordered as follows: MPs shape > Coagulant type > Coagulant dosage > MPs concentration > MPs size > MPs type > pH. Finally, knowledge gaps and potential future directions are proposed. This review assists in the understanding of the coagulation removal of MPs, and provides novel insight into the challenges posed by MPs in drinking water.

Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity.

T cells are often absent from human cancer tissues during both spontaneously induced immunity and therapeutic immunotherapy, even in the presence of a functional T cell-recruiting chemokine system, suggesting the existence of T cell exclusion mechanisms that impair infiltration. Using a genome-wide in vitro screening platform, we identified a role for phospholipase A2 group 10 (PLA2G10) protein in T cell exclusion. PLA2G10 up-regulation is widespread in human cancers and is associated with poor T cell infiltration in tumor tissues. PLA2G10 overexpression in immunogenic mouse tumors excluded T cells from infiltration, resulting in resistance to anti-PD-1 immunotherapy. PLA2G10 can hydrolyze phospholipids into small lipid metabolites, thus inhibiting chemokine-mediated T cell mobility. Ablation of PLA2G10's enzymatic activity enhanced T cell infiltration and sensitized PLA2G10-overexpressing tumors to immunotherapies. Our study implicates a role for PLA2G10 in T cell exclusion from tumors and suggests a potential target for cancer immunotherapy.

Enhanced enzymatic sugar production from corn stover by combination of water extraction and glycerol-assisted instant catapult steam explosion.

Glycerol-assisted instant catapult steam explosion (ICSE) of lignocellulose is an effective pretreatment method for enhancing sugar production compared to glycerol-free ICSE. In this study, glycerol-assisted ICSE of corn stover was studied in order to understand the reaction mechanisms and further optimize the process. Results showed that water extraction of corn stover prior to ICSE reduced pseudo-lignin formation. The combination of water extraction and glycerol-assisted ICSE led to the formation of lignin with a lower molecular weight (Mw) of 2851 g/mol than 3521 g/mole of that from the combination of water extraction and glycerol-free ICSE. 1H-13C NMR analysis revealed that glycerol likely reacted with lignin carboxylic OHs through esterification while etherification of aliphatic OHs was not observed in ICSE. These lignin analyses indicated that glycerol protected lignin from condensation/repolymerization during glycerol-assisted ICSE. Enzymatic hydrolysis results showed that without water extraction increasing glycerol usage from 0.2 kg/kg stover to 0.4 kg/kg stover improved glucan digestibility to 78% but further increase to 0.5 kg/kg stover reduced glucan digestibility. In addition, at the glycerol usage of 0.2-0.4 kg/kg stover, washing of pretreated stover for removal of glycerol and other biomass-derived compounds did not improve glucan digestibility compared to unwashed ones. Combination of water extraction and glycerol-assisted ICSE led to a high glucan digestibility of 89.7% and a total glucose yield of 25.5 g glucose/100 g stover, which were 30.1% and 7.5 g/100 g stover higher than those derived from glycerol-free ICSE of stover, respectively. Since glycerol is a low-cost carbon source, the resulting enzymatic hydrolysate that contained both glucose and glycerol may be directly used to produce bioproducts by microbial fermentation.

Effect of "Tiaoshen" acupuncture technique on mild depression and its underlying mechanism: A randomized controlled trial study protocol.

Background: Mild depression is not just a mental disease, but also a serious and long-term public health issue. It affects the quality of life of patients and can quickly develop into major depression. There are currently no effective drug treatments with high efficacy and few adverse reactions. Acupuncture may be an alternative treatment option. Preliminary experiments and practices have demonstrated that "Tiaoshen" acupuncture improves symptoms in patients who have depression, however the underlying data and method remain unclear at present. Methods: This is a prospective, single-center, single-blind, randomized controlled trial. We plan to recruit 70 participants and randomly assign them to receive "Tiaoshen" acupuncture or traditional acupuncture at a ratio of 1:1. Then, all the participants will receive the appropriate acupuncture treatment for four weeks. The results of the Hamilton Depression Rating Scale (HDSR-24) will serve as the primary outcome, while the results of the Patient Health Questionnaire-9 (PHQ-9) and the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) will serve as secondary outcomes. Evaluations will be conducted at baseline, 1, 2, and 4 weeks after treatment initiation, and 1 and 3 months after treatment completion. The safety of the intervention will be evaluated every week using the Columbia-Suicide Severity Rating Scale (C-SSRS) and the Treatment Emergent Symptoms Scale (TESS). Serum levels of oxidative stress markers 8-iso-prostaglandin F2α (8-iso-PGF2α), superoxide dismutase (SOD), uric acid (UA), and total bilirubin (TBIL) will be measured at baseline and the end of the treatment. We will conduct a statistical analysis of intention to treat (ITT) and conformance to protocol set (PPS) data. Discussion: This research aims to provide high-quality evidence for the efficacy and safety of "Tiaoshen" acupuncture as a treatment for mild depression. In addition, the mechanism through which acupuncture heals mild depression will be investigated.

Unlocking Enhanced Butadiene Selectivity: The Crucial Role of Zeolite Channel Confinement in the Selective Decarbonylation of γ-Valerolactone.

Herein, we report a highly selective production route for butadiene from γ-valerolactone over zeolite catalysts. The catalytic performance of eight zeolites with different framework topologies were compared, revealing that zeolites with narrower 10-membered ring channels exhibit enhanced selectivity of butadiene. Specifically, ZSM-35 and ZSM-22, featuring the narrowest 10-membered ring channels, demonstrate the highest butadiene selectivity to 61 % and 59 %, respectively. Notably, surface passivation of ZSM-35 leads to a remarkable increase in butadiene selectivity to 82 %, maintaining a 99 % conversion. Additionally, we propose a reaction network and identify cyclopentenone as a key intermediate in the transformation of γ-valerolactone to butadiene. Both experimental and theoretical results conclude that confinement effect of 10-membered ring channels improves the selectivity of butadiene.

Current research and evidence gaps on placental development in iron deficiency anemia.

Studying the effects of maternal iron deficiency anemia (IDA) is complex owing to its diverse causes, each independently impacting the placenta and fetus. Simple treatment with iron supplements does not always resolve the anemia. Therefore, delving into how IDA alters placental development at a molecular level is crucial to further optimize treatment. This review addresses the effects of IDA on placental structures and functions, including changes in oxygen levels, blood vessels, and the immune system. Profound understanding of physiological characteristics and regulatory mechanisms of placental development is key to explain the mechanisms of abnormal placental development in pregnancy-associated disorders. In turn, future strategies for the prevention and treatment of pregnancy complications involving the placenta can be devised. These studies are significant for improving human reproductive health, enhancing sociodemographic qualities, and even lifelong wellbeing, a focal point in future placental research.

Validation of a new kit for preeclampsia screening: A comprehensive analysis.

Objectives: Preeclampsia is a common pregnancy complication that significantly contributes to maternal mortality, perinatal mortality, and preterm delivery. The sFlt-1/PlGF (fms-like tyrosine kinase-1/placental growth factor) ratio has demonstrated robust diagnostic value for preeclampsia. This study assessed the analytical performance and diagnostic accuracy of a novel quantitative determination kit for sFlt-1 and PlGF for the diagnosis of preeclampsia. Methods: The detection performance of the test kit was validated using the Center for Medical Device Evaluation (CMDE) and Clinical and Laboratory Standards Institute (CLSI) documents. The test results were compared to those of the Elecsys immunoassay (Roche Diagnostics). Independent discovery and validation sets were used to analyze the diagnostic efficacy of the preeclampsia kit. The area under the curve (AUC) for preeclampsia at different gestational ages was calculated. Results: Correlation analysis between the test and Roche kits revealed a strong concordance (sFlt-1: r = 0.9966, P < 0.0001; PlGF: r = 0.9935, P < 0.0001). The AUCs for sFlt-1, PlGF, and the sFlt-1/PlGF ratio in diagnosing preeclampsia were 0.749, 0.795, and 0.834, respectively, in the discovery set and 0.729, 0.811, and 0.831, respectively, in the validation set. The corresponding results from the Roche kit were 0.741, 0.795, and 0.829, respectively, and 0.761, 0.864, and 0.844, respectively. Conclusions: Quantitative sFlt-1 and PlGF kits exhibited high levels of consistency with the Roche kits in terms of quantitative outcomes and diagnostic performance for preeclampsia.

Repeated Exposure Enhanced Toxicity of Clarithromycin on Microcystis aeruginosa Versus Single Exposure through Photosynthesis, Oxidative Stress, and Energy Metabolism Shift.

Antibiotics are being increasingly detected in aquatic environments, and their potential ecological risk is of great concern. However, most antibiotic toxicity studies involve single-exposure experiments. Herein, we studied the effects and mechanisms of repeated versus single clarithromycin (CLA) exposure on Microcystis aeruginosa. The 96 h effective concentration of CLA was 13.37 µg/L upon single exposure but it reduced to 6.90 µg/L upon repeated exposure. Single-exposure CLA inhibited algal photosynthesis by disrupting energy absorption, dissipation and trapping, reaction center activation, and electron transport, thereby inducing oxidative stress and ultrastructural damage. In addition, CLA upregulated glycolysis, pyruvate metabolism, and the tricarboxylic acid cycle. Repeated exposure caused stronger inhibition of algal growth via altering photosynthetic pigments, reaction center subunits biosynthesis, and electron transport, thereby inducing more substantial oxidative damage. Furthermore, repeated exposure reduced carbohydrate utilization by blocking the pentose phosphate pathway, consequently altering the characteristics of extracellular polymeric substances and eventually impairing the defense mechanisms of M. aeruginosa. Risk quotients calculated from repeated exposure were higher than 1, indicating significant ecological risks. This study elucidated the strong influence of repeated antibiotic exposure on algae, providing new insight into antibiotic risk assessment.

Mechanical strength changes of combustible municipal solid waste components during their early pyrolysis stage and mechanism analysis.

Implementation of municipal solid waste (MSW) source segregation leads to a more convenient recycle of combustible MSW components. Textiles, plastics and papers are commonly available combustible components in MSW. Their shredding is conducive to resources recovery. But these components usually have high tensile strengths and are difficult to shred. To understand their mechanical strength changes in their early pyrolysis stage will help to address this problem. In this study, a universal electronic testing machine was used to determine the breaking strengths of the materials including cotton towel, polyethylene glycol terephthalate (PET), ivory board (IB), kraft paper (KP) and wool scarf in the temperature range of 30-250°C under N2 atmosphere, and the mechanisms of their strength changes were explored. The reaction force field molecular dynamics (ReaxFF-MD) simulation was used to explain the decomposition behaviours of different sugar groups of hemicellulose in cotton and paper and the change of van der Waals energy of wool during their early pyrolysis stages. The results showed that breaking strengths of all the combustible MSW components reduced as the temperature increased. The breaking strength of PET was found to have the highest descent rate with increasing temperature, then the descent rates of wool and cotton came as the second and third, respectively. Compared with cotton, the breaking strengths of KP and IB decreased more slowly. As the temperature increased, the breaking strength of cotton reduced mainly due to the decomposition of the glucuronic acid in hemicellulose, and the reduction was characterized by CO2 release. The breaking strength reduction of PET was caused by its molecular chain being relaxed. The breaking strength reduction of wool was firstly caused by the decrease in the van der Waals energy between its molecules, and then caused by molecular chain breaking. In addition, in order to understand the influence of material size on the breaking strength change during thermal treatment, the breaking strengths of cotton yarn bundles were correlated with their yarn number and temperature. This study lays the foundation for understanding changes in mechanical strengths of combustible MSW components during their early pyrolysis stage.

Towards Human-like Walking with Biomechanical and Neuromuscular Control Features: Personalized Attachment Point Optimization Method of Cable-Driven Exoskeleton.

The cable-driven exoskeleton can avoid joint misalignment, and is substantial alterations in the pattern of muscle synergy coordination, which arouse more attention in recent years to facilitate exercise for older adults and improve their overall quality of life. This study leverages principles from neuroscience and biomechanical analysis to select attachment points for cable-driven soft exoskeletons. By extracting key features of human movement, the objective is to develop a subject-specific design methodology that provides precise and personalized support in the attachment points optimization of cable-driven exoskeleton to achieve natural gait, energy efficiency, and muscle coordination controllable in the domain of human mobility and rehabilitation. To achieve this, the study first analyzes human walking experimental data and extracts biomechanical features. These features are then used to generate trajectories, allowing better natural movement under complete cable-driven exoskeleton control. Next, a genetic algorithm-based method is employed to minimize energy consumption and optimize the attachment points of the cable-driven system. This process identifies connections that are better suited for the human model, leading to improved efficiency and natural movement. By comparing the calculated elderly human model driven by exoskeleton with experimental subject in terms of joint angles, joint torques and muscle forces, the human model can successfully replicate subject movement and the cable output forces can mimic human muscle coordination. The optimized cable attachment points facilitate more natural and efficient collaboration between humans and the exoskeleton, making significant contributions to the field of assisting the elderly in rehabilitation.

"Baihui" (DU20)-penetrating "Qubin" (GB7) acupuncture on blood-brain barrier integrity in rat intracerebral hemorrhage models via the RhoA/ROCK II/MLC 2 signaling pathway.

BACKGROUND: Blocking the RhoA/ROCK II/MLC 2 (Ras homolog gene family member A/Rho kinase II/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the RhoA/ROCK II/MLC 2 signaling pathway changes the pathogenic processes of the blood-brain barrier (BBB) after intracerebral hemorrhage (ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH. METHODS: Scalp acupuncture (SA) therapy was performed on rats with ICH at the acupuncture point "Baihui"-penetrating "Qubin," and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the RhoA/ROCK II/MLC 2 signaling pathway. Post-assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging. RESULTS: We found that ROCK II acts as a promoter of the RhoA/ROCK II/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the pre-intervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK II, a 7-day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at "Baihui"-penetrating "Qubin" and treatment with fasudil could improve the expression of endothelial-related proteins by inhibiting the RhoA/ROCK II/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats. CONCLUSION: This study found that these experimental data indicated that SA at "Baihui"-penetrating "Qubin" could preserve BBB integrity and neurological function recovery after ICH by inhibiting RhoA/ROCK II/MLC 2 signaling pathway activation and by regulating endothelial cell-related proteins.

Comparison of immune-related gene signatures and immune infiltration features in early- and late-onset preeclampsia.

BACKGROUND: Preeclampsia, a severe pregnancy syndrome, is widely accepted divided into early- and late-onset preeclampsia (EOPE and LOPE) based on the onset time of preeclampsia, with distinct pathophysiological origins. However, the molecular mechanism especially immune-related mechanisms for EOPE and LOPE is currently obscure. In the present study, we focused on placental immune alterations between EOPE and LOPE and search for immune-related biomarkers that could potentially serve as potential therapeutic targets through bioinformatic analysis. METHODS: The gene expression profiling data was obtained from the Gene Expression Omnibus database. ESTIMATE algorithm and Gene Set Enrichment Analysis were employed to evaluate the immune status. The intersection of differentially expressed genes in GSE74341 series and immune-related genes set screened differentially expressed immune-related genes. Protein-protein interaction network and random forest were used to identify hub genes with a validation by a quantitative real-time PCR. Kyoto Encyclopedia of Genes and Genomes pathways, Gene Ontology and gene set variation analysis were utilized to conduct biological function and pathway enrichment analyses. Single-sample gene set enrichment analysis and CIBERSORTx tools were employed to calculate the immune cell infiltration score. Correlation analyses were evaluated by Pearson correlation analysis. Hub genes-miRNA network was performed by the NetworkAnalyst online tool. RESULTS: Immune score and stromal score were all lower in EOPE samples. The immune system-related gene set was significantly downregulated in EOPE compared to LOPE samples. Four hub differentially expressed immune-related genes (IL15, GZMB, IL1B and CXCL12) were identified based on a protein-protein interaction network and random forest. Quantitative real-time polymerase chain reaction validated the lower expression levels of four hub genes in EOPE compared to LOPE samples. Immune cell infiltration analysis found that innate and adaptive immune cells were apparent lacking in EOPE samples compared to LOPE samples. Cytokine-cytokine receptor, para-inflammation, major histocompatibility complex class I and T cell co-stimulation pathways were significantly deficient and highly correlated with hub genes. We constructed a hub genes-miRNA regulatory network, revealing the correlation between hub genes and hsa-miR-374a-5p, hsa-miR-203a-3p, hsa-miR-128-3p, hsa-miR-155-3p, hsa-miR-129-2-3p and hsa-miR-7-5p. CONCLUSIONS: The innate and adaptive immune systems were severely impaired in placentas of EOPE. Four immune-related genes (IL15, GZMB, IL1B and CXCL12) were closely correlated with immune-related pathogenesis of EOPE. The result of our study may provide a new basis for discriminating between EOPE and LOPE and acknowledging the role of the immune landscape in the eventual interference and tailored treatment of EOPE.

Bridging the gap: Geometry-centric discriminative manifold distribution alignment for enhanced classification in colorectal cancer imaging.

The early detection of colorectal cancer (CRC) through medical image analysis is a pivotal concern in healthcare, with the potential to significantly reduce mortality rates. Current Domain Adaptation (DA) methods strive to mitigate the discrepancies between different imaging modalities that are critical in identifying CRC, yet they often fall short in addressing the complexity of cancer's presentation within these images. These conventional techniques typically overlook the intricate geometrical structures and the local variations within the data, leading to suboptimal diagnostic performance. This study introduces an innovative application of the Discriminative Manifold Distribution Alignment (DMDA) method, which is specifically engineered to enhance the medical image diagnosis of colorectal cancer. DMDA transcends traditional DA approaches by focusing on both local and global distribution alignments and by intricately learning the intrinsic geometrical characteristics present in manifold space. This is achieved without depending on the potentially misleading pseudo-labels, a common pitfall in existing methodologies. Our implementation of DMDA on three distinct datasets, involving several unique DA tasks, has consistently demonstrated superior classification accuracy and computational efficiency. The method adeptly captures the complex morphological and textural nuances of CRC lesions, leading to a significant leap in domain adaptation technology. DMDA's ability to reconcile global and local distributional disparities, coupled with its manifold-based geometrical structure learning, signals a paradigm shift in medical imaging analysis. The results obtained are not only promising in terms of advancing domain adaptation theory but also in their practical implications, offering the prospect of substantially improved diagnostic accuracy and faster clinical workflows. This heralds a transformative approach in personalized oncology care, aligning with the pressing need for early and accurate CRC detection.

CS/CoFe2O4 nanocomposite as a high-effective and steady chainmail catalyst for tetracycline degradation with peroxymonosulfate activation: performance and mechanism.

Tetracycline becomes a crucial measure for managing and treating communicable diseases in both human and animal sectors due to its beneficial antibacterial properties and cost-effectiveness. However, it is important not to trivialize the associated concerns of environmental contamination following the antibiotic's application. In this study, cobalt ferrate (CoFe2O4) nanoparticles were loaded into chitosan (CS), which can avoid the agglomeration problem caused by high surface energy and thus improve the catalytic performance of cobalt ferrate. And it can avoid the problem of secondary contamination caused by the massive leaching of metal ions. The resulting product was used as a catalyst to activate peroxymonosulfate (PMS) for the degradation of tetracycline (TC). To determine the potential effects on TC degradation, various factors such as PMS dosing, catalyst dosing, TC concentration, initial solution pH, temperature, and inorganic anions (Cl-, H2PO4- and HCO3-) were investigated. The CS/CoFe2O4/PMS system exhibited superior performance compared to the CoFe2O4-catalyzed PMS system alone, achieving a 92.75% TC removal within 120 min. The catalyst displayed high stability during the recycling process, with the efficiency observed after five uses remaining at a stable 73.1%, and only minor leaching of dissolved metal ions from the catalyst. This confirms the high stability of the catalyst. The activation mechanism study showed that there are free radical and non-free radical pathways in the reaction system to degrade TC together, and SO4•- and 1O2 are the primary reactive oxygen radicals involved in the reaction, allowing for effective treatment of contaminated water by TC.