Vertical spatial denitrification performance and microbial community composition in denitrification biofilters coupled with water electrolysis.

In this study, a denitrification biofilter coupled with water electrolysis (DNBF-WE) was developed as a novel heterotrophic-hydrogen autotrophic denitrification system, which could enhance denitrification with limited organic carbon in the secondary effluent. The volumetric denitrification rate of DNBF-WE reached 152.16 g N m-3 d-1 (C/N = 2, I = 60 mA, and HRT = 5 h). Besides, the vertical spatial denitrification of DNBF-WE was explored, with the nitrate removal rate being 49.5%, 16.3%, and 29.3% in the top, middle, and bottom, respectively. The concentration of extracellular polymeric substances (EPSs) was consistent with the denitrification performance vertically. The high-throughput sequencing analysis results revealed that autotrophic denitrification bacteria (e.g. Thauera) gradually enriched along DNBF-WE from top to bottom. The functional gene prediction results illustrated the vertical stratification mechanisms of the denitrification. Both dissimilatory nitrate reduction and denitrification contributed to nitrate removal, and denitrification became more advantageous with an increase in the filter depth. The research on both the performance of DNBF-WE and the characteristics of microbial communities in the vertical zones of the biofilter may lay a foundation for the biofilter denitrification process in practice.

The protective role of prebiotics and probiotics on diarrhea and gut damage in the rotavirus-infected piglets.

Rotavirus is one of the pathogenic causes that induce diarrhea in young animals, especially piglets, worldwide. However, nowadays, there is no specific drug available to treat the disease, and the related vaccines have no obvious efficiency in some countries. Via analyzing the pathogenesis of rotavirus, it inducing diarrhea is mainly due to disturb enteric nervous system, destroy gut mucosal integrity, induce intracellular electrolyte imbalance, and impair gut microbiota and immunity. Many studies have already proved that prebiotics and probiotics can mitigate the damage and diarrhea induced by rotavirus infection in hosts. Based on these, the current review summarizes and discusses the effects and mechanisms of prebiotics and probiotics on rotavirus-induced diarrhea in piglets. This information will highlight the basis for the swine production utilization of prebiotics and probiotics in the prevention or treatment of rotavirus infection in the future.

Molecular cloning and characterization of a salt overly sensitive3 (SOS3) gene from the halophyte Pongamia.

A high concentration of sodium (Na+) is the primary stressor for plants in high salinity environments. The Salt Overly Sensitive (SOS) pathway is one of the best-studied signal transduction pathways, which confers plants the ability to export too much Na+ out of the cells or translocate the cytoplasmic Na+ into the vacuole. In this study, the Salt Overly Sensitive3 (MpSOS3) gene from Pongamia (Millettia pinnata Syn. Pongamia pinnata), a semi-mangrove, was isolated and characterized. The MpSOS3 protein has canonical EF-hand motifs conserved in other calcium-binding proteins and an N-myristoylation signature sequence. The MpSOS3 gene was significantly induced by salt stress, especially in Pongamia roots. Expression of the wild-type MpSOS3 but not the mutated nonmyristoylated MpSOS3-G2A could rescue the salt-hypersensitive phenotype of the Arabidopsis sos3-1 mutant, which suggested the N-myristoylation signature sequence of MpSOS3 was required for MpSOS3 function in plant salt tolerance. Heterologous expression of MpSOS3 in Arabidopsis accumulated less H2O2, superoxide anion radical (O2-), and malondialdehyde (MDA) than wild-type plants, which enhanced the salt tolerance of transgenic Arabidopsis plants. Under salt stress, MpSOS3 transgenic plants accumulated a lower content of Na+ and a higher content of K+ than wild-type plants, which maintained a better K+/Na+ ratio in transgenic plants. Moreover, no development and growth discrepancies were observed in the MpSOS3 heterologous overexpression plants compared to wild-type plants. Our results demonstrated that the MpSOS3 pathway confers a conservative salt-tolerant role and provided a foundation for further study of the SOS pathway in Pongamia.

Risk factors and clinical prediction models for prolonged mechanical ventilation after heart valve surgery.

OBJECTIVES: Prolonged mechanical ventilation (PMV) is a common complication following cardiac surgery linked to unfavorable patient prognosis and increased mortality. This study aimed to search for the factors associated with the occurrence of PMV after valve surgery and to develop a risk prediction model. METHODS: The patient cohort was divided into two groups based on the presence or absence of PMV post-surgery. Comprehensive preoperative and intraoperative clinical data were collected. Univariate and multivariate logistic regression analyses were employed to identify risk factors contributing to the incidence of PMV. Based on the logistic regression results, a clinical nomogram was developed. RESULTS: The study included 550 patients who underwent valve surgery, among whom 62 (11.27%) developed PMV. Multivariate logistic regression analysis revealed that age (odds ratio [OR] = 1.082, 95% confidence interval [CI] = 1.042-1.125; P < 0.000), current smokers (OR = 1.953, 95% CI = 1.007-3.787; P = 0.047), left atrial internal diameter index (OR = 1.04, 95% CI = 1.002-1.081; P = 0.041), red blood cell count (OR = 0.49, 95% CI = 0.275-0.876; P = 0.016), and aortic clamping time (OR = 1.031, 95% CI = 1.005-1.057; P < 0.017) independently influenced the occurrence of PMV. A nomogram was constructed based on these factors. In addition, a receiver operating characteristic (ROC) curve was plotted, with an area under the curve (AUC) of 0.782 and an accuracy of 0.884. CONCLUSION: Age, current smokers, left atrial diameter index, red blood cell count, and aortic clamping time are independent risk factors for PMV in patients undergoing valve surgery. Furthermore, the nomogram based on these factors demonstrates the potential for predicting the risk of PMV in patients following valve surgery.

Exploring work readiness: A qualitative descriptive study of self-perceptions among new graduate nurses.

Background: Reduced work readiness is associated with elevated turnover rates, necessitating efforts to enhance the positive work readiness of newly graduated nurses to alleviate the shortage in the nursing workforce. Research into the work readiness of recent nursing graduates in China is still in its infancy. Most studies employ quantitative research methods, and further exploration of the self-perception of work readiness among new nurses in China is required. Objectives: This study aimed to investigate genuine experiences and self-perceptions of work readiness among new graduate nurses. Design: A qualitative descriptive study. Methods: Sixteen new nurses from a provincial tertiary hospital in China were included in this study, which adhered to the consolidated criteria for reporting qualitative research (COREQ) checklist for reporting. The data collection process involved conducting semi-structured interviews from September to October 2021. Inductive content analysis was employed to analyze the interview data. Results: The study identified four themes encompassing new nurses' real-life experiences and self-perceptions of work readiness: psychological stress, emotional conflict, empathy fatigue, and ethical dilemmas. Psychological stress comprised three subthemes: knowledge and skill deficits, communication barriers, and fear. Empathy fatigue was primarily characterized by psychological and physical symptoms. Ethical dilemmas involved conflicts over differences in values and between clinical reality and standardized nursing practice. Conclusion: Drawing from the self-perceptions of work readiness among new nurses found in this study, nursing administrators and educators must enhance the existing transition support program for new nurses. Additionally, the establishment of individualized training programs is recommended to further improve the work readiness of new nurses.

MpNAC1, a transcription factor from the mangrove associate Millettia pinnata, confers salt and drought stress tolerance in transgenic Arabidopsis and rice.

Pongamia (Millettia pinnata Syn. Pongamia pinnata), a mangrove associate plant, exhibits good stress tolerance, making it a treasure of genetic resources for crop improvement. NAC proteins are plant-specific transcription factors, which have been elucidated to participate in the regulation and tolerance of abiotic stresses (such as salt and drought). Here, we identified a salt-induced gene from Pongamia, MpNAC1, which encodes an NAC factor sharing five highly conserved domains with other NACs and exhibits close homology to AtNAC19/AtNAC55/AtNAC72 in Arabidopsis. MpNAC1 showed nuclear localization and transcriptional activator activity. MpNAC1-overexpressing Arabidopsis exhibited significantly stronger salt and drought tolerance compared with wild-type plants. The expression levels of stress-responsive genes were activated in transgenic Arabidopsis. Furthermore, the heterologous expression of MpNAC1 also enhanced the salt and drought tolerance of transgenic rice. The major agronomic traits, such as plant height and tiller number, panicle length, grain size, and yield, were similar between the transgenic lines and wild type under normal field growth conditions. RNA-Seq analysis revealed that MpNAC1 significantly up-regulated stress-responsive genes and activated the biosynthesis of secondary metabolites such as flavonoids, resulting in increased stress tolerance. Taken together, the MpNAC1 increased salt and drought stress tolerance in transgenic plants and did not retard the plant growth and development under normal growth conditions, suggesting the potential of MpNAC1 in breeding stress-resilient crops.

Taurine ameliorates sensorimotor function by inhibiting apoptosis and activating A2 astrocytes in mice after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a form of severe acute stroke with very high mortality and disability rates. Early brain injury (EBI) and delayed cerebral ischemia (DCI) contribute to the poor prognosis of patients with SAH. Currently, some researchers have started to focus on changes in amino acid metabolism that occur in brain tissues after SAH. Taurine is a sulfur-containing amino acid that is semi-essential in animals, and it plays important roles in various processes, such as neurodevelopment, osmotic pressure regulation, and membrane stabilization. In acute stroke, such as cerebral hemorrhage, taurine plays a neuroprotective role. However, the role of taurine after subarachnoid hemorrhage has rarely been reported. In the present study, we established a mouse model of SAH. We found that taurine administration effectively improved the sensorimotor function of these mice. In addition, taurine treatment alleviated sensorimotor neuron damage and reduced the proportion of apoptotic cells. Furthermore, taurine treatment enhanced the polarization of astrocytes toward the neuroprotective phenotype while inhibiting their polarization toward the neurotoxic phenotype. This study is the first to reveal the relationship between taurine and astrocyte polarization and may provide a new strategy for SAH research and clinical treatment.

Exploring trade-offs between residential and industrial functions in rural areas and their ecological impacts across transitioning agricultural systems: Evidence from the metropolitan suburbs of China.

The rapid transition of agricultural systems substantially affects residential and industrial land use systems in rural areas, often generating spatiotemporal trade-offs between residential and industrial functions and producing considerable ecological impacts, which has thus far not been well understood. We conduct an indicator-based assessment of transitioning agriculture systems, and then links the transitioning agricultural systems to trade-offs between residential and industrial functions from 2005 to 2020 by using a case study-the metropolitan suburbs of Beijing, China. Also, the associated ecological impacts of the trade-offs are characterized based on the calculation of the ecological quality index (EQI) and ecological contribution rate. The results show that trade-offs between residential and industrial functions in the metropolitan suburbs have gradually adapted to the different agricultural systems in transition, which can be characterized by increasing industrial function as well as declining residential function, together with the diversification of land use into a mixed pattern. Additionally, along with the transitioning process comes a U shape of the ecological quality curve, which indicates that relentless industrial sprawl into regions where the agricultural system has a low capacity for technology, as well as decay in rural areas attributed to a rural exodus and industrial decline in semi-subsistence agricultural areas, even cause ecological degradation. In general, trade-offs between residential and industrial functions (especially for the non-agricultural production function) in rural areas could partially and temporally generate unfavorable ecological impacts, but it seems to be a favorable phenomenon to promote ecological quality in the long term. Therefore, to achieve rural sustainable planning, it is necessary for land use management to observe the trade-offs between residential and industrial functions while avoiding negative impacts, such as low-density land use patterns, disordered land use functions, and eco-environmental deterioration. Such effective strategies can contribute to the feasible implementation of policies aiming to achieve the compatible development of liveable residences, highly efficient industrial production, and eco-friendly operations in rural areas.

Protective effect of Broussonetia papyrifera leaf polysaccharides on intestinal integrity in a rat model of diet-induced oxidative stress.

This study aimed to investigate the effect of Broussonetia papyrifera polysaccharides (BPP) on the jejunal intestinal integrity of rats ingesting oxidized fish oil (OFO) induced oxidative stress. Polysaccharides (Mw 16,956 Da) containing carboxyl groups were extracted from Broussonetia papyrifera leaves. In vitro antioxidant assays showed that this polysaccharide possessed antioxidant capabilities. Thirty-two male weaned rats were allocated into two groups orally infused BPP solution and PBS for 26 days, respectively. From day 9 to day 26, half of the rats in each group were fed food containing OFO, where the lipid peroxidation can induce intestinal oxidative stress. OFO administration resulted in diarrhea, decreased growth performance (p < 0.01), impaired jejunal morphology (p < 0.05) and antioxidant capacity (p < 0.01), increased the levels of ROS and its related products, IL-1ß and IL-17 (p < 0.01) of jejunum, as well as down-regulated Bcl-2/Bax (p < 0.01) and Nrf2 signaling (p < 0.01) of jejunum in rats. BPP gavage effectively alleviated the negative effects of OFO on growth performance, morphology, enterocyte apoptosis, antioxidant capacity and inflammation of jejunum (p < 0.05) in rats. In the oxidative stress model cell assay, the use of receptor inhibitors inhibited the enhancement of antioxidant capacity by BPP. These results suggested that BPP protected intestinal morphology, thus improving growth performance and reducing diarrhea in rats ingesting OFO. This protective effect may be attributed to scavenging free radicals and activating the Nrf2 pathway, which enhances antioxidant capacity, consequently reducing inflammation and mitigating intestinal cell death.

Icephobic Durability of Molecular Brush-Structured PDMS Soft Coatings.

The accumulation of ice can pose numerous inconveniences and potential hazards, profoundly affecting both human productivity and daily life. To combat the challenges posed by icing, extensive research efforts have been dedicated to the development of low-ice adhesion surfaces. In this study, we harness the power of molecular dynamics simulations to delve into the intricate dynamics of polymer chains and their role in determining the modulus of the material. We present a novel strategy to prepare ultralow-modulus poly(dimethylsiloxane) (PDMS) elastomers with a molecular brush configuration as icephobic materials. The process involves grafting monohydride-terminated PDMS (H-PDMS) as side chains onto backbone chain PDMS with pendant vinyl functional groups to yield a molecular brush structure. The segments of this polymer structure effectively restrict interchain entanglement, thereby rendering a lower modulus compared to traditional linear structures at an equivalent cross-linking density. The developed soft coating exhibits a remarkably ultralow ice adhesion strength of 13.1 ± 1.1 kPa. Even after enduring 50 cycles of icing and deicing, the ice adhesion strength of this coating steadfastly stayed below 16 kPa, showing no notable increase. Importantly, the molecular brush coating applied to glass demonstrated an impressive light transmittance of 92.1% within the visible light spectrum, surpassing the transmittance of bare glass, which was measured at 91.3%. This icephobic coating with exceptional light transmittance offers a wide range of applications and holds significant potential as a practical icephobic material.

CSF N-acylethanolamine acid amidase level and Parkinson's disease risk: A mendelian randomization study.

BACKGROUND: Neuroinflammation is involved in the progression of Parkinson's disease (PD), and N-acylethanolamine acid amidase (NAAA) is involved in regulating inflammation by hydrolyzing bioactive lipid mediators called N-acylethanolamines (NAEs). However, the causal relationship between cerebrospinal fluid (CSF) NAAA protein levels and the risk of PD remains unclear. This study aimed to explore the causal effect of CSF NAAA levels on PD risk through Mendelian randomization (MR) analysis. METHOD: Genome-wide association study (GWAS) summary statistics for CSF NAAA protein quantitative trait loci (pQTL) and GWAS summary statistics for PD were obtained from publicly available databases. Inverse-variance weighted (IVW) was the main causal estimation method for MR analysis. In addition, the maximum likelihood, MR Egger regression, and weighted median were used to supplement the IVW results. Finally, various sensitivity tests were performed to verify the reliability of the MR findings. RESULTS: In the initial MR analysis, the IVW showed that CSF NAAA protein levels significantly increased PD risk (odds ratio [OR] = 1.17, 95% confidence interval [CI]: 1.01-1.35, P = 0.031). This finding was further validated in a replicate MR analysis (OR = 1.20, 95% CI: 1.02-1.41, P = 0.027). Sensitivity analysis showed that MR results were stable and not affected by heterogeneity and horizontal pleiotropy. CONCLUSION: The present MR study supports a causal relationship between elevated CSF NAAA protein levels and increased PD risk.

Mechanism of Pressure Difference Variations on Heavy Oil Start-Up and Percolation Effects.

To investigate the influence of pressure difference changes on the micro start-up and percolation of heavy oil, a micro visualization displacement device was used to characterize the start-up time and oil-water percolation state of heavy oil. The mechanism of different pressure differences, as well as the frequency and amplitude of pressure difference changes, on the start-up and percolation balance of heavy oil was clarified. The results indicate that high-pressure difference and pressure difference changes can reduce the start-up time of heavy oil. A reasonable frequency of pressure difference changes effectively promotes the balance between positive and negative pressure shear and fluid-solid response. Large pressure difference changes can effectively break the viscous and adsorption resistance during heavy oil start-up; reasonable pressure difference can exert the synergistic effect of pressure difference and infiltration, achieving a balance between the water wave and the initial water film thickening process as well as the continuous percolation process of wire drawing, oil droplets, and oil columns during the medium-to-high water content period; a reasonable frequency of pressure difference variation during the high water content period can promote the superposition of inertia effects at the oil-water interface and break the balance of the oil-water interface. A large amplitude of pressure difference variation is beneficial for the strong deformation of the oil-water interface and the shear dislocation peeling of the oil-solid interface. Therefore, a relatively high amplitude of pressure difference variation and a reasonable frequency of pressure difference variation, as well as the synergistic effect of pressure difference and infiltration, are the keys to effectively start heavy oil and improving oil recovery during the ultrahigh water-cut period.

Nicotinamide ribose ameliorates myocardial ischemia/reperfusion injury by regulating autophagy and regulating oxidative stress.

Nicotinamide riboside (NR) has been reported to play a protective role in myocardial ischemia-reperfusion (I/R) injury when used in association with other drugs; however, the individual effect of NR is unknown. In the present study Evan's blue/triphenyl tetrazolium chloride staining, hematoxylin and eosin staining, echocardiography, western blotting, reverse transcription-quantitative PCR, and the detection of myocardial injury-associated markers and oxidative stress metabolites were used to explore the ability of NR to alleviate cardiac I/R injury and the relevant mechanisms of action. In a mouse model of I/R injury, dietary supplementation with NR reduced the area of myocardial ischemic infarction, alleviated pathological myocardial changes, decreased inflammatory cell infiltration and attenuated the levels of mitochondrial reactive oxygen species (ROS) and creatine kinase myocardial band (CK-MB). In addition, echocardiography suggested that NR alleviated the functional damage of the myocardium caused by I/R injury. In H9c2 cells, NR pretreatment reduced the levels of lactate dehydrogenase, CK-MB, malondialdehyde, superoxide dismutase and ROS, and reduced cell mortality after the induction of hypoxia/reoxygenation (H/R) injury. In addition, the results indicated NR activated sirt 1 via the upregulation of nicotinamide adenine dinucleotide (NAD+) and protected the cells against autophagy. The sirt 1 inhibitor EX527 significantly attenuated the ability of NR to inhibit autophagy, but had no significant effect on the ROS content of the H9c2 cells. In summary, the present study suggests that NR protects against autophagy by increasing the NAD+ content in the body via the sirt 1 pathway, although the sirt 1 pathway does not affect oxidative stress.

ACBP4-WRKY70-RAP2.12 module positively regulates submergence-induced hypoxia response in Arabidopsis thaliana.

ACYL-CoA-BINDING PROTEINs (ACBPs) play crucial regulatory roles during plant response to hypoxia, but their molecular mechanisms remain poorly understood. Our study reveals that ACBP4 serves as a positive regulator of the plant hypoxia response by interacting with WRKY70, influencing its nucleocytoplasmic shuttling in Arabidopsis thaliana. Furthermore, we demonstrate the direct binding of WRKY70 to the ACBP4 promoter, resulting in its upregulation and suggesting a positive feedback loop. Additionally, we pinpointed a phosphorylation site at Ser638 of ACBP4, which enhances submergence tolerance, potentially by facilitating WRKY70's nuclear shuttling. Surprisingly, a natural variation in this phosphorylation site of ACBP4 allowed A. thaliana to adapt to humid conditions during its historical demographic expansion. We further observed that both phosphorylated ACBP4 and oleoyl-CoA can impede the interaction between ACBP4 and WRKY70, thus promoting WRKY70's nuclear translocation. Finally, we found that the overexpression of orthologous BnaC5.ACBP4 and BnaA7.WRKY70 in Brassica napus increases submergence tolerance, indicating their functional similarity across genera. In summary, our research not only sheds light on the functional significance of the ACBP4 gene in hypoxia response, but also underscores its potential utility in breeding flooding-tolerant oilseed rape varieties.

Attenuation of neuronal ferroptosis in intracerebral hemorrhage by inhibiting HDAC1/2: Microglial heterogenization via the Nrf2/HO1 pathway.

AIM: The class I histone deacetylases (HDACs) implicate in microglial heterogenization and neuroinflammation following Intracerebral hemorrhage (ICH). Ferroptosis has also been reported in the ICH model. However, the relationship between HDAC1/2's role in microglial heterogenization and neuronal ferroptosis remains unclear. METHODS: In both in vivo and in vitro models of ICH, we used Romidepsin (FK228), a selective HDAC1/2 inhibitor, to investigate its effects on microglial heterogenization and neuronal ferroptosis. In the in vitro ICH model using Hemin, a transwell system was utilized to examine how microglia-driven inflammation and ICH-triggered neuronal ferroptosis interact. Immunostaining, Western blotting and RT-qPCR were used to evaluate the microglial heterogenization and neuronal ferroptosis. Microglial heterogenization, neuronal ferroptosis, and neurological dysfunctions were assessed in vivo ICH mice model performed by autologous blood injection. RESULTS: HDAC1/2 inhibition altered microglial heterogenization after ICH, as showing the reducing neuroinflammation and shifting microglia towards an anti-inflammatory phenotype by immunostaining and qPCR results. HDAC1/2 inhibition reduced ferroptosis, characterized by high ROS and low GPx4 expression in HT22 cells, and reduced iron and lipid deposition post-ICH in vivo. Additionally, the Nrf2/HO1 signaling pathway, especially acetyl-Nrf2, activated in the in vivo ICH model due to HDAC1/2 inhibition, plays a role in regulating microglial heterogenization. Furthermore, HDAC1/2 inhibition improved sensorimotor and histological outcomes post-ICH, offering a potential mechanism against ICH. CONCLUSION: Inhibition of HDAC1/2 reduces neuro-ferroptosis by modifying the heterogeneity of microglia via the Nrf2/HO1 pathway, with a particular focus on acetyl-Nrf2. Additionally, this inhibition aids in the faster removal of hematomas and lessens prolonged neurological impairments, indicating novel approach for treating ICH.

Kornblum Oxidation Reaction-Induced Collective Transformation of Lead Polyhalides for Stable Perovskite Photovoltaics.

The iodide vacancy defects generated during the perovskite crystallization process are a common issue that limits the efficiency and stability of perovskite solar cells (PSCs). Although excessive ionic iodides have been used to compensate for these vacancies, they are not effective in reducing defects through modulating the perovskite crystallization. Moreover, these iodide ions present in the perovskite films can act as interstitial defects, which are detrimental to the stability of the perovskite. Here, an effective approach to suppress the formation of vacancy defects by manipulating the coordination chemistry of lead polyhalides during perovskite crystallization is demonstrated. To achieve this suppression, an α-iodo ketone is introduced to undergo a process of Kornblum oxidation reaction that releases halide ions. This process induces a rapid collective transformation of lead polyhalides during the nucleation process and significantly reduces iodide vacancy defects. As a result, the ion mobility is decreased by one order of magnitude in perovskite film and the PSC achieves significantly improved thermal stability, maintaining 82% of its initial power conversion efficiency at 85 °C for 2800 h. These findings highlight the potential of halide ions released by the Kornblum oxidation reaction, which can be widely used for achieving high-performance perovskite optoelectronics.

Spatiotemporal transformable nano-assembly for on-demand drug delivery to enhance anti-tumor immunotherapy.

Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy, but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration. Herein, we designed a cancer-associated fibroblasts (CAFs) triggered structure-transformable nano-assembly (HSD-P@V), which can directionally deliver valsartan (Val, CAFs regulator) and doxorubicin (DOX, senescence inducer) to the specific targets. In detail, DOX is conjugated with hyaluronic acid (HA) via diselenide bonds (Se-Se) to form HSD micelles, while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer, which is coated on Val nanocrystals (VNs) surface for improving the stability and achieving responsive release. Once arriving at tumor microenvironment and touching CAFs, HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment. VNs can degrade the extracellular matrix, leading to the enhanced penetration of HSD. HSD targets tumor cells, releases DOX to induce senescence, and recruits effector immune cells. Furthermore, senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy. In vitro and in vivo results show that the nano-assembly remarkably inhibits tumor growth as well as lung metastasis, and extends tumor-bearing mice survival. This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.

Preliminary study of the role of nanobacteria in the formation of renal stones in experimental rats and its mechanism.

Introduction: The aim of the study was to study the role of nanobacteria in the formation of renal calculi and the underlying mechanism. Material and methods: A total of 90 clean Wistar male rats were randomly divided into a negative control group, an experimental group, and an interference group. From the end of the first week of modelling, 10 consecutive times once a week, 3 rats in each group were randomly selected to measure the biochemical blood markers and urine metabolism. After sacrifice, the formation of kidney stones was assessed by observing the ultrastructure of the kidney by electron microscopy and pathohistology. Finally, the expression of calcium-sensitive receptor (CaSR) and claudin-14 protein in the kidney tissue was examined by western blotting. Results: Compared with the control group, the gross structure of the kidney was changed in the model group. At the fourth week of modelling, the rats in the nanobacteria group had significantly enlarged kidneys and increased kidney-to-body ratio, and the difference had statistical significance (p < 0.05). The colour of the kidney profile was dark, the structure of the skin pulp was less clear, and the accumulation of yellowish particles was observed at the junction of the cortical pulp. The creatinine, uric acid, urea nitrogen, and urinary calcium of the rats in the nanobacteria group began to increase at the third week, and the difference between the third and eighth week had statistical significance (p < 0.05). However, the difference between the 3 groups had no statistical significance after the eighth week. At the fourth week, we observed the formation of calculi, which were mainly distributed in the renal tubules and surrounding tissues. The kidney stone formation rate was 52.4% in the nanobacteria group and 27.8% in the interference group, and the difference had statistical significance (p < 0.05). Ultrastructure observations revealed that from the fourth week, the renal tissues in the nanobacteria group showed expanded renal tubules, swollen renal tubular epithelium, granular degeneration, shedding and lymphocyte infiltration of renal tubular epithelial cells, and a small amount of calcium salt crystals in renal tubules. At the third week, the expression of CaSR and Claudin-14 protein in the nanobacteria group increased, and the difference had statistical significance (p < 0.05). The expression of CaSR and Claudin-14 was positively correlated with urinary calcium (p < 0.05). Conclusions: The formation of renal calculi began in the fourth week after the model was established, and the crystals were mostly located in the renal tubules. During the formation of renal calculi, the renal tubular epithelial cells were damaged, showing granular degeneration and small amounts of calcium salt crystals, accompanied by a few renal tubules beginning to expand and epithelial swelling, granular degeneration, necrosis and shedding of renal tubular epithelial cells, lymphocyte infiltration in the renal interstitium, and small amounts of calcium salt crystals in the renal tubules, which aggravated with time. The serum creatinine, serum uric acid, urea nitrogen, and urinary calcium levels increased with time from the third week and returned to normal after the eighth week. The expression of CaSR and Claudin-14 protein was upregulated and positively correlated with the 24-h urinary calcium excretion value.

Switching of brain networks across different cerebral perfusion states: insights from EEG dynamic microstate analyses.

The alteration of neural interactions across different cerebral perfusion states remains unclear. This study aimed to fulfill this gap by examining the longitudinal brain dynamic information interactions before and after cerebral reperfusion. Electroencephalogram in eyes-closed state at baseline and postoperative 7-d and 3-month follow-ups (moyamoya disease: 20, health controls: 23) were recorded. Dynamic network analyses were focused on the features and networks of electroencephalogram microstates across different microstates and perfusion states. Considering the microstate features, the parameters were disturbed of microstate B, C, and D but preserved of microstate A. The transition probabilities of microstates A-B and B-D were increased to play a complementary role across different perfusion states. Moreover, the microstate variability was decreased, but was significantly improved after cerebral reperfusion. Regarding microstate networks, the functional connectivity strengths were declined, mainly within frontal, parietal, and occipital lobes and between parietal and occipital lobes in different perfusion states, but were ameliorated after cerebral reperfusion. This study elucidates how dynamic interaction patterns of brain neurons change after cerebral reperfusion, which allows for the observation of brain network transitions across various perfusion states in a live clinical setting through direct intervention.

Melittin analog p5RHH enhances recombinant adeno-associated virus transduction efficiency.

OBJECTIVE: Melittin and its derivative have been developed to support effective gene delivery systems. Their ability to facilitate endosomal release enhances the delivery of nanoparticle-based gene therapy. Nevertheless, its potential application in the context of viral vectors has not received much attention. Therefore, we would like to optimize the rAAV vector by Melittin analog to improve the transduction efficiency of rAAV in liver cancer cells and explore the mechanism of Melittin analog on rAAV. METHODS: Various melittin-derived peptides were inserted into loop VIII of the capsid protein in recombinant adeno-associated virus vectors. These vectors carrying either gfp or fluc genes were subjected to quantitative polymerase chain reaction assays and transduction assays in human embryonic kidney 293 (HEK293T) cells to investigate the efficiency of vector production and gene delivery. In addition, the ability of a specific p5RHH-rAAV vector to deliver genes was examined through in vitro transduction of different cultured cells and in vivo tail vein administration to C57BL/6 mice. Finally, the intricate details of the vector-mediated transduction mechanisms were explored by using pharmacological inhibitors of every stage of the rAAV2 intracellular life cycle. RESULTS: A total of 76 melittin-related peptides were identified from existing literature. Among them, CMA-3, p5RHH and aAR3 were found to significantly inhibit transduction of rAAV2 vector crude lysate. The p5RHH-rAAV2 vectors efficiently transduced not only rAAV-potent cell lines but also cell lines previously considered resistant to rAAV. Mechanistically, bafilomycin A1, a vacuolar endosome acidification inhibitor, completely inhibited the transgene expression mediated by the p5RHH-rAAV2 vectors. Most importantly, p5RHH-rAAV8 vectors also increased hepatic transduction in vivo in C57BL/6 mice. CONCLUSION: The incorporation of melittin analogs into the rAAV capsids results in a significant improvement in rAAV-mediated transgene expression. While further modifications remain an area of interest, our studies have substantially broadened the pharmacological prospects of melittin in the context of viral vector-mediated gene delivery. Please cite this article as: Meng J, He Y, Yang H, Zhou L, Wang S, Feng X, Al-shargi OY, Yu X, Zhu L, Ling, C. Melittin analog p5RHH enhances recombinant adeno-associated virus transduction efficiency. J Integr Med. 2024; 22(1): 72-82.