Two three-dimensional coordination polymers as fluorescence probes for the detection of nitrobenzene, tetracycline, fluazinam and their application in green pepper.

Two coordination polymers (CPs), [Zn5(L)2(phen)5](1) and [Cd2(HL)(2,2-bpy)(H2O)3](2), were synthesized by using 2',3,3',5,5'-Diphenyl ether pentacarboxylic acid (H5L), phenanthroline (phen), and 2,2'-bipyridine (2,2'-bpy) under hydrothermal conditions. The L5- ligand adopts the µ6-к2: к2: к1: к1: к1: к1 mode in 1 and the µ5-к2: к2: к2: к2: к1 mode in 2. Sensing experiments show that 1 and 2 are fluorescence probes with high sensitivity and rapid detection of nitro explosives, antibiotics, and pesticides. In order to verify the ability of 2 to detect FLU in actual samples, we performed a spiked recovery experiment in green pepper water. The spiked recoveries were 97.77-101.18 %. Interestingly, because H5L is not completely deprotonated in 2, there is abundant hydrogen bonding, which makes the fluorescence quenching rate higher and the detection limit lower. The possible fluorescence quenching mechanism of 1 and 2 can be explained by their UV-VIS absorption spectra and orbital energy levels.

Deciphering the natural and anthropogenic drivers on the fate and risk of antibiotics and antibiotic resistance genes (ARGs) in a typical river-estuary system, China.

This study conducts an in-depth assessment of the spatial distribution, ecological risks, and correlations among 12 antibiotics, antibiotic resistance genes (ARGs), and dominant microorganisms in a representative river-estuary system, classified by land use and hydrodynamic conditions. Sulfonamides and quinolones were identified as the major contaminants in surface waters, with aquaculture and healthcare wastewater responsible for over 80 % of the antibiotic load. Contrasting seasonal patterns were observed between freshwater (wet season: 215 ng/L, dry season: 99.9 ng/L) and tidal estuaries (wet season: 45.9 ng/L, dry season: 121 ng/L), attributed to antibiotic transport from terrestrial sources or coastal aquaculture areas. The estimated annual antibiotic influx into Jiaozhou Bay was 70.4 kg/year, posing a considerable threat to aquatic algae and disrupting the stability of aquatic food chain. BugBase predictions suggested that antibiotics in the environment suppressed bacteria characterized by biofilm formation (FB) and the presence of mobile elements (CME). However, ARG transmission was likely to drive the spread of CME, FB, and stress-tolerant (OST) bacteria within microbial communities. The significant positive correlations observed between sulfamethoxazole and 63 microbial genera indicate a broad distribution of microbial resistance, which exacerbates the potential for ARG accumulation and dissemination across both the bay and the Yellow Sea.

Catestatin as a predictor for cardiac death in heart failure with mildly reduced and preserved ejection fraction.

AIMS: Endogenous catecholamine release-inhibitory peptide catestatin has been associated with heart failure (HF). This subgroup analysis of our cohort of HF compared the different effects of catestatin as a predictor for cardiac outcomes in patients with HF with reduced (HFrEF), mildly reduced (HFmrEF) or preserved (HFpEF) ejection fraction. METHODS: Plasma catestatin was measured in the HF patient cohort of 228 cases with a whole spectrum of ejection fraction. The cardiac deaths were analysed according to prespecified subgroups. RESULTS: Over a median follow-up of 52.5 months, the association between plasma catestatin and cardiac death was different in patients with HFrEF, HFmrEF or HFpEF [hazard ratio (HR) 1.53, 95% confidence interval (CI) 0.99-2.37 and HR 2.73, 95% CI 1.56-4.75, respectively; interaction P = 0.022]. Patients with HFmrEF/HFpEF were older and more likely to be female, with non-ischaemic cardiomyopathy and atrial fibrillation but lower levels of plasma B-type natriuretic peptide (BNP). Similar adverse cardiac events occurred in patients with HFmrEF/HFpEF as in HFrEF. Plasma catestatin was a better predictor for cardiovascular death in the HFmrEF/HFpEF patients [area under the receiver operating characteristic curve (AUC) = 0.72, 95% CI 0.45-0.74] than in the HFrEF patients (AUC = 0.59, 95% CI 0.587-0.849). The optimal cut point of plasma catestatin level of 0.86 ng/mL predicted a 2.80-fold elevated risk for cardiac death in HFmrEF/HFpEF. CONCLUSIONS: Elevated plasma catestatin might be a more sensitive predictor for cardiac outcome in patients with HFmrEF/HFpEF than in HFrEF.

Inflammation-related markers and prognosis of alpha-fetoprotein producing gastric cancer.

BACKGROUND: Inflammation-related markers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI) and prognostic nutritional index (PNI) could reflect tumor immune microenvironment and predict prognosis of cancers. However, it had not been explored in alpha-fetoprotein (AFP) producing gastric cancer (GC). AIM: To determine the predictive value of inflammation-related peripheral blood markers including as NLR, PLR, MLR, SII, SIRI and PNI in the prognosis of AFP- producing GC (AFPGC). Besides, this study would also compare the differences in tumor immune microenvironment, clinical characteristics and prognosis between AFPGC and AFP- GC patients to improve the understanding of this disease. METHODS: 573 patients enrolled were retrospectively studied. They were divided into AFP+ group (AFP ≥ 20 ng/mL) and AFP- group (AFP < 20 ng/mL), comparing the levels of NLR/PLR/MLR/SII/SIRI/PNI and prognosis. In AFP+ group, the impact of NLR/PLR/MLR/SII/SIRI/PNI and their dynamic changes on prognosis were further explored. RESULTS: Compared with AFP- patients, AFP+ patients had higher NLR/PLR/MLR/SII/SIRI and lower PNI levels and poorer overall survival (OS). In the AFP+ group, mortality was significantly lower in the lower NLR/PLR/MLR/SII/SIRI group and higher PNI group. Moreover, the dynamic increase (NLR/PLR/MLR/SII/SIRI) or decrease (PNI) was associated with the rise of mortality within 1 year of follow-up. CONCLUSION: Compared with AFP- patients, the level of inflammation-related peripheral blood markers significantly increased in AFP+ patients, which was correlated with OS of AFP+ patients. Also, the gradual increase of SII and SIRI was associated with the risk of death within one year in AFP+ patients. AFPGC should be considered as a separate type and distinguished from AFP- GC because of the difference in tumor immune microenvironment. It requires basic experiments and large clinical samples in the future.

Electrochemical detection of poly(ADP-ribose) polymerase-1 with silver nanoparticles as signal labels by integrating the advantages of homogeneous reaction with surface-tethered detection.

Poly(ADP-ribose)polymerase-1 (PARP1) could be activated by binding to nucleic acids with specific sequences, thus catalyzing the poly-ADP-ribosylation (PARylation) of target proteins including PARP1 itself. Most of the previously reported electrochemical methods for the determination of PARP1 were relied on the electrostatic interactions, which required the pre-immobilization of DNA on an electrode for the capture of PARP1. Herein, we reported an "immobilization-free" electrochemical strategy for the assays of PARP1 on the basic of avidin-biotin interaction. Once PARP1 was activated by binding with the specific double-stranded DNA (dsDNA) in a homogeneous solution, the biotinylated nicotinamide adenine dinucleotide (biotin-NAD+) was transferred onto PARP1, resulting in the formation of biotinylated PAR polymers. The resulting biotinylated PAR polymers were then captured by a neutravidin (NA)-modified electrode through avidin-biotin interactions. The rich biotin moieties in the PAR polymers allowed for the capture of NA-modified silver nanoparticles (NA-AgNPs) through the avidin-biotin interactions. The surface-tethered AgNPs produced a well-defined electrochemical signal due to the characteristic solid-state Ag/AgCl process. The "immobilization-free", electrostatic interaction-independent electrochemical biosensor exhibited low background current, high sensitivity, and good stability. It has achieved the determination of PARP1 with a detection limit down to 0.7 mU. The biosensor was further applied to determine the inhibition efficiency of potential inhibitors with a satisfactory result. This method shows promising potential applications in PARP1-related clinical diagnosis and drug discovery.

Targeting NPM1 inhibits proliferation and promotes apoptosis of hepatic progenitor cells via suppression of mTOR signalling pathway.

BACKGROUND: Hepatic progenitor cells serve not only as the origin of combined hepatocellular cholangiocarcinoma (cHCC-CCA) but are also responsible for malignancy recurrence after surgical resection. Nucleophosmin 1 (NPM1) has been implicated in cancer metastasis and poor prognosis. This study aimed to determine the expression of NPM1 by hepatic progenitor cells in cHCC-CCA and the effects of targeting NPM1 on hepatic progenitor cells and BEL-7402 cells with characteristics of both progenitor cells and cHCC-CCA. METHODS: First, NPM1 was detected by RT‒PCR, western blotting, and double-immunofluorescence staining in cHCC-CCA tissues. NPM1 expression was subsequently analysed in rat hepatic progenitor cells cultured in vitro and in interleukin 6 (IL6)-treated cells. The effects and mechanism of NPM1 on hepatic progenitor cells were determined by knocking down NPM1 and performing RNA sequencing analysis. Finally, NSC348884, a small-molecule inhibitor that disrupts NPM1 dimer formation, was used to confirm the function of NPM1 in BEL-7402 cells. RESULTS: Both human hepatic progenitor cells in cHCC-CCA tissues and rat in vitro cultured hepatic progenitor cells highly expressed NPM1. IL6, a cytokine involved in the malignant transformation of hepatic progenitor cells, dose-dependently increased NPM1 and PCNA expression. Knocking down NPM1 reduced IL6R transcription (P < 0.0001) and inhibited the proliferation (P = 0.0065) of hepatic progenitor cells by suppressing the mTOR signalling pathway and activating the apoptosis pathway. Furthermore, knocking down NPM1 in hepatic progenitor cells resulted in more apoptotic cells (7.33 ± 0.09% vs. 3.76 ± 0.13%, P < 0.0001) but fewer apoptotic cells in the presence of NSC348884 (47.57 ± 0.49% vs. 63.40 ± 0.05%, P = 0.0008) than in the control cells, suggesting that low-NPM1-expressing cells are more resistant to NSC348884. In addition, NSC348884 induced the apoptosis of BEL-7402 cells with an IC50 of 2.77 µmol/L via the downregulation of the IL-6R and mTOR signalling pathways and inhibited the growth of BEL-7402 cells in a subcutaneous xenograft tumour model (P = 0.0457). CONCLUSIONS: Targeting NPM1 inhibits proliferation and induces apoptosis in hepatic progenitor cells and BEL-7402 cells, thus serving as a potential therapy for cHCC-CCA.

Intracellular zinc protects tumours from T cell-mediated cytotoxicity.

Tumour immune evasion presents a significant challenge to the effectiveness of cancer immunotherapies. Recent advances in high-throughput screening techniques have uncovered that loss of antigen presentation and cytokine signalling pathways are central mechanisms by which tumours evade T cell immunity. To uncover additional vulnerabilities in tumour cells beyond the well-recognized antigen presentation pathway, we conducted a genome-wide CRISPR/Cas9 screen to identify genes that mediate resistance to chimeric-antigen receptor (CAR)-T cells, which function independently of classical antigen presentation. Our study revealed that loss of core-binding factor subunit beta (CBFß) enhances tumour cell resistance to T cell killing, mediated through T cell-derived TNF. Mechanistically, RNA-sequencing and elemental analyses revealed that deletion of CBFß disrupts numerous pathways including those involved in zinc homoeostasis. Moreover, we demonstrated that modulation of cellular zinc, achieved by supplementation or chelation, significantly altered tumour cell susceptibility to TNF by regulating the levels of inhibitor of apoptosis proteins. Consistent with this, treatment of tumour cells with a membrane-permeable zinc chelator had no impact on tumour cell viability alone, but significantly increased tumour cell lysis by CD8+ T cells in a TNF-dependent but perforin-independent manner. These results underscore the crucial role of intracellular zinc in regulating tumour cell susceptibility to T cell-mediated killing, revealing a novel vulnerability in tumour cells that might be exploited for the development of future cancer immunotherapeutics.

Predicting drug-target interactions by measuring confidence with consistent causal neighborhood interventions.

Predicting drug-target interactions (DTI) is a crucial stage in drug discovery and development. Understanding the interaction between drugs and targets is essential for pinpointing the specific relationship between drug molecules and targets, akin to solving a link prediction problem using information technology. While knowledge graph (KG) and knowledge graph embedding (KGE) methods have been rapid advancements and demonstrated impressive performance in drug discovery, they often lack authenticity and accuracy in identifying DTI. This leads to increased misjudgment rates and reduced efficiency in drug development. To address these challenges, our focus lies in refining the accuracy of DTI prediction models through KGE, with a specific emphasis on causal intervention confidence measures (CI). These measures aim to assess triplet scores, enhancing the precision of the predictions. Comparative experiments conducted on three datasets and utilizing 9 KGE models reveal that our proposed confidence measure approach via causal intervention, significantly improves the accuracy of DTI link prediction compared to traditional approaches. Furthermore, our experimental analysis delves deeper into the embedding of intervention values, offering valuable insights for guiding the design and development of subsequent drug development experiments. As a result, our predicted outcomes serve as valuable guidance in the pursuit of more efficient drug development processes.

Highly active manganese nitride-europium nitride catalyst for ammonia synthesis.

The development of efficient catalysts for ammonia synthesis under mild conditions is critical for establishing a carbon-neutral society powered by renewable ammonia. While significant effort has been focused on Fe and Ru-based catalysts, there have been very limited studies on manganese-based catalysts for ammonia synthesis because of their low intrinsic catalytic activity. Herein, we report that the synergy between manganese nitride (Mn4N) and europium nitride (EuN) yields an ammonia synthesis rate that is 41 and 25 times higher than that of neat Mn4N and EuN, respectively. Detailed studies suggest that a [Eu-N-Mn] species at the interface of Mn4N and EuN plays a pivotal role in ammonia synthesis. Compositing of Mn4N with other rare earth metal nitrides such as LaN, PrN, and CeN also leads to a significant enhancement in catalytic activity. This work broadens the scope of advanced nitride catalysts for ammonia synthesis.

Expression of a novel hydrolase MhpC in Brevibacillus parabrevis BCP-09 and its characteristics for degrading synthetic pyrethroids.

Synthetic pyrethroids are widely used insecticides which may cause chronic diseases in non-target organisms upon long-term exposure. Microbial degradation offers a reliable method to remove them from the environment. This study focused on Brevibacillus parabrevis BCP-09 and its enzymes for degrading pyrethroids. The predicted deltamethrin-degrading genes phnA and mhpC were used to construct recombinant plasmids. These plasmids, introduced into Escherichia coli BL21(DE3) cells and induced with L-arabinose. The results indicated that the intracellular crude enzyme efficiently degraded deltamethrin by 98.8 %, ß-cypermethrin by 94.84 %, and cyfluthrin by 73.52 % within 24 h. The hydrolytic enzyme MhpC possesses a catalytic triad Ser/His/Asp and a typical "Gly-X-Ser-X-Gly" conservative sequence of the esterase family. Co-cultivation of induced E. coli PhnA and E. coli MhpC resulted in degradation rates of 41.44 ± 3.55 % and 60.30 ± 4.55 %, respectively, for deltamethrin after 7 d. This study states that the degrading enzymes from B. parabrevis BCP-09 are an effective method for the degradation of pyrethroids, providing available enzyme resources for food safety and environmental protection.

Risk hotspots and influencing factors identification of heavy metal(loid)s in agricultural soils using spatial bivariate analysis and random forest.

Heavy metal(loid)s (HMs) in agricultural soils not only affect soil function and crop security, but also pose health risks to residents. However, previous concerns have typically focused on only one aspect, neglecting the other. This lack of a comprehensive approach challenges the identification of hotspots and the prioritization of factors for effective management. To address this gap, a novel method incorporating spatial bivariate analysis with random forest was proposed to identify high-risk hotspots and the key influencing factors. A large-scale dataset containing 2995 soil samples and soil HMs (As, Cd, Cr, Cu, Mn, Ni, Pb, Sb, and Zn) was obtained from across Henan province, central China. Spatial bivariate analysis of both health risk and ecological risks revealed risk hotspots. Positive matrix factorization model was initially used to investigate potential sources. Twenty-two environmental variables were selected and input into random forest to further identify the key influencing factors impacting soil accumulation. Results of local Moran's I index indicated high-high HM clusters at the western and northern margins of the province. Hotspots of high ecological and health risk were primarily observed in Xuchang and Nanyang due to the widespread township enterprises with outdated pollution control measures. As concentration and exposure frequency dominated the non-carcinogenic and carcinogenic risks. Anthropogenic activities, particularly vehicular traffic (contributing ∼37.8 % of the total heavy metals accumulation), were the dominant sources of HMs in agricultural soils. Random forest modeling indicated that soil type and PM2.5 concentrations were the most influencing natural and anthropogenic variables, respectively. Based on the above findings, control measures on traffic source should be formulated and implemented provincially; in Xuchang and Nanyang, scattered township enterprises with outdated pollution control measures should be integrated and upgraded to avoid further pollution from these sources.

Implementation of a New Classification and Stratification System for Solitary Bone Tumor: Osseous Tumor Radiological and Interpretation and Management System (OT-RIMS).

OBJECTIVES: To propose a histological-grades-based Osseous Tumor Radiological Interpretation and Management System (OT-RIMS) that would simplify the radiological evaluation of bone tumors, categorize key radiological features into severity levels, and inform corresponding patient management actions. METHODS: This retrospective study between January 2015 and August 2022 evaluated patients with solitary bone tumors confirmed by pathology and imaging follow-up received two or three imaging modalities of radiographs, CT, or MRI. Three radiologists independently assessed radiological features, categorized bone lesions based on OT-RIMS criteria, and reached a consensus. Kappa statistics and observed agreement were calculated. RESULTS: A total of 341 patients (mean age, 26.0 years; 159 women) were included, with 102 malignant, 177 benign, and 62 intermediate or low-grade malignant bone lesions. Sensitivity and specificity of readers 1, 2, and 3, respectively, in the identification of malignant tumors into OT-RIMS 4 were 93.1% (95 of 102) and 93.3% (223 of 239), 96.1% (98 of 102) and 91.6% (219 of 239), 92.2% (94 of 102) and 89.5% (214 of 239). Inter-reader agreement of OT-RIMS category for three readers was considered excellent (Kendall's W = 0.924, p < 0.001) with a kappa value of reproducibility in categories 1&2, 3, and 4 of 0.764, 0.528, and 0.930, respectively. CONCLUSION: The OT-RIMS category demonstrated excellent reproducibility despite the reader's expertise level in categorizing the risk stratification of bone tumors and informing patient management, with histological grades used as the reference standard. ADVANCES IN KNOWLEDGE: The OT-RIMS category reliably stratifies bone tumors into four categories corresponding to histological grades and standardized patient management.

Effectiveness of internet-based self-help interventions for depression in adolescents and young adults: a systematic review and meta-analysis.

OBJECTIVE: To assess the effectiveness of Internet-based self-help interventions in treating depression in adolescents and young adults. METHODS: A systematic search was conducted across six databases, including PubMed, to identify randomized controlled trials (RCTs) that satisfied the specified inclusion and exclusion criteria. The intervention measure consisted of Internet-based self-help interventions. RESULTS: A total of 23 randomized controlled trials (RCTs) were included in this analysis. Meta-analysis indicated that Internet-based self-help therapies significantly reduced depression scores in adolescents and young adults. (OR = -0.68, 95%CI [-0.88, -0.47], P < 0.001). We examined the effects of patient recruitment from various regions, medication usage, therapist involvement, weekly intervention time, and intervention duration. Patients selected from school, primary healthcare centers, clinics and local communities had better results. Intervention lasting 30 to 60 min and 60 to180 minutes per week were effective in the short term. CONCLUSION: The internet-based self-help intervention can be effective in treating depression in adolescents and young adults. However, factors such as patient recruitment locations, medication usage, Therapists' involvement, weekly intervention time, and intervention duration interacted with the outcome. Subgroup analysis on potential adverse effects and gender was impossible due to insufficient data from the included studies.

Associations between social support and proactive health behaviours among Chinese adolescents: the mediating role of self-efficacy and peer relationships.

BACKGROUND: Proactive health behaviours are crucial for enhancing adolescent health. However, there is limited evidence on the potential pathways through which social support influences adolescents' proactive health behaviours. This cross-sectional study aimed to examine the relationships between social support, self-efficacy, peer relationships and proactive health behaviours in Chinese adolescents. METHODS: From October to December 2023, we recruited 6075 adolescents from Shandong Province, China. They completed self-report questionnaires on social support, self-efficacy, peer relationships and proactive health behaviours. RESULTS: Linear regression analysis indicated that social support was positively associated with proactive health behaviours among adolescents (ß = 0.571, 95% CI = 0.542, 0.600). Further mediation analyses revealed that self-efficacy (ß = 0.085, 95% CI = 0.069,0.101) and peer relationships (ß = 0.156, 95% CI = 0.136,0.177) mediated this relationship. CONCLUSIONS: Increased social support was associated with better proactive health behaviours in Chinese adolescents. Additionally, higher self-efficacy and positive peer relationships enhanced this association. Our findings emphasised the significance of providing supportive environments at home and at school to promote proactive health behaviours in adolescents.

MFG-E8 Ameliorates Nerve Injury-Induced Neuropathic Pain by Regulating Microglial Polarization and Neuroinflammation via Integrin ß3/SOCS3/STAT3 Pathway in Mice.

Spinal microglial polarization plays a crucial role in the pathological processes of neuropathic pain following peripheral nerve injury. Accumulating evidence suggests that milk fat globule epidermal growth factor-8 (MFG-E8) exhibits anti-inflammatory effect and regulates microglial polarization through the integrin ß3 receptor. However, the impact of MFG-E8 on microglial polarization in the context of neuropathic pain has not yet been investigated. In this study, we evaluated the effect of MFG-E8 on pain hypersensitivity and spinal microglial polarization following spared nerve injury (SNI) of the sciatic nerve in mice. We determined the molecular mechanisms underlying the effects of MFG-E8 on pain hypersensitivity and spinal microglial polarization using pain behavior assessment, western blot (WB) analysis, immunofluorescence (IF) staining, quantitative polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), and small interfering RNA (siRNA) transfection. Our findings indicate that SNI significantly increased the levels of MFG-E8 and integrin ß3 expressed in microglia within the spinal cord of mice. Additionally, we observed that intrathecal injection of recombinant human MFG-E8 (rhMFG-E8) alleviated SNI induced-mechanical allodynia and thermal hyperalgesia. Furthermore, the results suggested that rhMFG-E8 facilitated M2 microglial polarization and ameliorated neuroinflammation via integrin ß3/SOCS3/STAT3 pathway in the spinal cord of mice with SNI. Importantly, these effects were negated by integrin ß3 siRNA, or SOCS3 siRNA. These results demonstrate that MFG-E8 ameliorates peripheral nerve injury induced-mechanical allodynia and thermal hyperalgesia by driving M2 microglial polarization and mitigating neuroinflammation mediated by integrin ß3/SOCS3/STAT3 pathway in the spinal cord of mice. MFG-E8 may serve as a promising target for the treatment of neuropathic pain.

Impacts of February climate conditions in the Gobi Desert on March dust activities in the northern East Asia.

Amid ongoing global warming, intense dust storms continue to plague regions despite efforts to understand and mitigate their impacts. This study explores the connection between surface temperature (ST) and precipitation (PRE) in the Gobi Desert (GD) during February and their subsequent effects on March dust concentrations across northern East Asia. Our analysis reveals a clear pattern: higher February ST combined with lower PRE in GD correlates with increased dust levels in March, with ST effects predominantly in northern areas of dust sources compared to PRE. The warming of the ST in February facilitates surface thawing, and the concurrently reduced PRE decreases soil moisture in GD. These conditions both contribute to the loosening of the soil, thereby creating favorable lower boundary conditions for the onset of dust activities in the subsequent March. Atmospheric dynamics play a pivotal role in the changes of ST and PRE. The preceding ST warming is closely tied to the weakening of the East Asian winter monsoon. Furthermore, the Eurasia teleconnection (EU) pattern is identified as a key circulation factor driving the changes of February PRE in GD. Additionally, sea surface temperature anomalies in the Barents Sea and the North Atlantic appear to influence these atmospheric circulation changes, altering ST and PRE in GD, and consequently, impacting March dust dynamics in northern East Asia. This study provides crucial insights into the climatic precursors that drive dust storm activities, which are essential for improving the accuracy of dust storm forecasting.

p75ECD-Fc reverses neonatal hypoxic-ischemic encephalopathy-induced neurological deficits and inhibits apoptosis associated with Nestin.

A recent study has introduced a recombinant fusion protein, consisting of the extracellular domain (ECD) of p75 and the Fc fragment of human immunoglobulin IgG1 (p75ECD-Fc), as a multifaceted agent within the nervous system. This research aimed to assess the effects of p75ECD-Fc on neuronal growth and the restoration of neurological functions in rats afflicted with neonatal hypoxic-ischemic encephalopathy (NHIE). In vitro analyses revealed that 1 µM p75ECD-Fc treatment markedly increased cell viability and facilitated neurite outgrowth in neurons exposed to oxygen-glucose deprivation (OGD). Subsequent in vivo studies determined that a dose of 78.6 µg/3 µl of p75ECD-Fc significantly mitigated brain damage and both acute and long-term neurological impairments, outperforming the therapeutic efficacy of hypothermia, as evidenced through behavioral assessments. Additionally, in vivo immunostaining showed that p75ECD-Fc administration enhanced neuronal survival and regeneration, and reduced astrocytosis and microglia activation in the cortex and hippocampus of NHIE rats. A noteworthy shift from A1 to A2 astrocyte phenotypes and from M1 to M2 microglia phenotypes was observed after p75ECD-Fc treatment. Furthermore, a co-expression of the p75 neurotrophin receptor (p75NTR) and Nestin was identified, with an overexpression of Nestin alleviating the neurological dysfunction induced by NHIE. Mechanistically, the neuroprotective effects of p75ECD-Fc, particularly its inhibition of neuronal apoptosis post-OGD, may be attributed to Nestin. Taken together, these results highlight the neuroprotective and anti-inflammatory effects of p75ECD-Fc treatment through the modulation of glial cell phenotypes and the Nestin-mediated inhibition of neuronal apoptosis, positioning it as a viable therapeutic approach for NHIE.

Scanning sample-specific miRNA regulation from bulk and single-cell RNA-sequencing data.

BACKGROUND: RNA-sequencing technology provides an effective tool for understanding miRNA regulation in complex human diseases, including cancers. A large number of computational methods have been developed to make use of bulk and single-cell RNA-sequencing data to identify miRNA regulations at the resolution of multiple samples (i.e. group of cells or tissues). However, due to the heterogeneity of individual samples, there is a strong need to infer miRNA regulation specific to individual samples to uncover miRNA regulation at the single-sample resolution level. RESULTS: Here, we develop a framework, Scan, for scanning sample-specific miRNA regulation. Since a single network inference method or strategy cannot perform well for all types of new data, Scan incorporates 27 network inference methods and two strategies to infer tissue-specific or cell-specific miRNA regulation from bulk or single-cell RNA-sequencing data. Results on bulk and single-cell RNA-sequencing data demonstrate the effectiveness of Scan in inferring sample-specific miRNA regulation. Moreover, we have found that incorporating the prior information of miRNA targets can generally improve the accuracy of miRNA target prediction. In addition, Scan can contribute to construct cell/tissue correlation networks and recover aggregate miRNA regulatory networks. Finally, the comparison results have shown that the performance of network inference methods is likely to be data-specific, and selecting optimal network inference methods is required for more accurate prediction of miRNA targets. CONCLUSIONS: Scan provides a useful method to help infer sample-specific miRNA regulation for new data, benchmark new network inference methods and deepen the understanding of miRNA regulation at the resolution of individual samples.

miR827 orchestrates the regulation of SPX-MFS1 and SPX-MFS5 with the assistance of lncRNA767 to enhance phosphate starvation tolerance and maize development.

MicroRNA827 (miR827) is functionally conserved among different plant species and displays species-specific characteristics, but the mechanisms by which miR827 regulates phosphate (Pi) starvation tolerance and maize development remain elusive. We found that miR827 selectively targets the Pi transporter genes SPX-MFS1 and SPX-MFS5. miR827 overexpression improved the Pi starvation tolerance, plant architecture and grain yield and quality, whereas miR827 suppression yielded a contrasting phenotype. In addition, we identified a specific long noncoding RNA (lncRNA767) that serves as a direct target and a facilitator of miR827 and can stabilize the SPX-MFS1 and SPX-MFS5 transcripts, leading to their translation inhibition. The orchestrated regulation of SPX-MFS1 and SPX-MFS5 modulates PHR1; 1 and PHR1; 2, which are critical transcription factors in Pi signalling, and thereby affects the expression of downstream Pi starvation-induced genes. Together, these findings demonstrate that miR827, assisted by lncRNA767, enhances SPX-MFS1 and SPX-MFS5 suppression and thus exerts a significant impact on Pi homeostasis and several essential agronomic traits of maize.

Analysis on slope stability by anchorage based on soil creep with flood effect.

In order to analyze the adverse effect of flood affection on slope stability, the analytical expressions of buoyancy force and capillary force, hydrodynamic pressure and impact force, and scour erosion were proposed based on the aging characteristics of soil shear strength and limit equilibrium theory. According to the load combination and flood action, shear failure occurs preferentially at the foot of slope. Then, the plastic zone continues to extend upward to produce traction landslide disaster mode. Furthermore, the power function relation between shear strength index and time was established. The nonlinear accelerated creep model was also obtained. At the same time, the safety factor formula for flood loading effect slope aging stability, the time-varying characteristic value of anchor force and the compensation value of anchor force were also obtained and used to research sliding mechanism. In addition, the numerical calculation example shows that the slope safety factor decreases by more than 20 % considering the effect of flood ascending scour and impact, and the compensation value of anchorage force increases obviously with time increasing. Simultaneously, the change rate of compensation value of anchorage force increases nonlinearly with the increase of design safety factor.