[Rapid Start-up of Continuous Autotrophic Nitrogen Removal Reactor by Hybrid-inoculating PN and PN/A Granular Sludges].

The rapid cultivation of partial nitritation/ANAMMOX （PN/A） granular sludge in a continuous-flow mode is one of the key technologies for efficient biological nitrogen removal in domestic wastewater treatment. Compared with that in PN/A granular sludge, PN granular sludge demonstrates a shorter incubation period and suitability for batch culture. It is also a good carrier for enriching ANAMMOX （AMX） bacteria. In this study, we established a continuous-flow autotrophic nitrogen removal process in three continuously stirred tank reactors （CSTR） （R1-R3） by hybrid-inoculating PN/A and PN granular sludge at the mass ratios of 3∶1, 1∶1, and 1∶3, respectively. By implementing high ammonium nitrogen loading and short hydraulic retention time, continuous autotrophic nitrogen removal processes were successfully started up in the three CSTRs. The results showed that compared with that of R1 and R2, R3 had a longer start-up time but a similar steady-state nitrogen removal performance. The total nitrogen removal load of R3 could be more than 2.6 kg·ï¼ˆm3·d）-1. Intriguingly, the inoculated PN granular sludge served as a precursor for PN/A granular sludge cultivation. This approach facilitated the enrichment of anaerobic ammonia-oxidizing bacteria （AMX） by introducing abundant ammonium-oxidizing bacteria （AOB） and nitrite nitrogen substrates into the CSTR. According to the results of high-throughput sequencing, the microbial abundance and diversity of the mature granules in R1-R3 were significantly higher than those of the inoculation sludge. AOB （genus Nitrosomonas）, AMX （genera Candidatus Kuenenia and Candidatus Brocadia）, and symbiotic heterotrophs, such as Chloroflexi, Bacteroidetes, and Chlorobi, drove the autotrophic nitrogen removal process and maintained the stability of the granular structure. In summary, a novel start-up strategy of hybrid-inoculating granular sludge was provided for a continuous-flow autotrophic nitrogen removal in engineering application.

Therapeutic potential of microglia-derived extracellular vesicles in ischemic stroke.

Ischemic stroke (IS) is a debilitating neurological disorder with limited treatment options. Extracellular vesicles (EVs) have emerged as crucial lipid bilayer particles derived from various cell types that facilitate intercellular communication and enable the exchange of proteins, lipids, and genetic material. Microglia are resident brain cells that play a crucial role in brain development, maintenance of neuronal networks, and injury repair. They secrete numerous extracellular vesicles in different states. Recent evidence indicates that microglia-derived extracellular vesicles (M-EVs) actively participate in mediating various biological processes, such as neuroprotection and neurorepair, in stroke, making them an excellent therapeutic approach for treating this condition. This review comprehensively summarizes the latest research on M-EVs in stroke and explores their potential as novel therapeutic targets for this disorder. Additionally, it provides an overview of the effects and functions of M-EVs on stroke recovery to facilitate the development of clinically relevant therapies for IS.

A pH ultra-sensitive hydrated iridium oxyhydroxide films electrochemical sensor for label-free detection of Vibrio parahaemolyticus.

Vibrio parahaemolyticus (V. parahaemolyticus) is a major foodborne pathogen, which can cause serious foodborne illnesses like diarrhoea. Rapid on-site detection of foodborne pathogens is an ideal way to respond to foodborne illnesses. Herein, we provide an electrochemical sensor for rapid on-site detection. This sensor utilized a pH-sensitive metal-oxide material for the concurrent isothermal amplification and label-free detection of nucleic acids. Based on a pH-sensitive hydrated iridium oxide oxyhydroxide film (HIROF), the electrode transforms the hydrogen ion compound generated during nucleic acid amplification into potential, so as to achieve a real-time detection. The results can be transmitted to a smartphone via Bluetooth. Moreover, HIROF was applied in nucleic acid device detection, with a super-Nernst sensitivity of 77.6 mV/pH in the pH range of 6.0-8.5, and the sensitivity showed the best results so far. Detection of V. parahaemolyticus by this novel method showed a detection limit of 1.0 × 103 CFU/mL, while the time consumption was only 30 min, outperforming real-time fluorescence loop-mediated isothermal amplification (LAMP). Therefore, the characteristics of compact, portable, and fast make the sensor more widely used in on-site detection.

Assembly of root-associated bacterial community and soil health in cadmium-contaminated soil affected by nano/bulk-biochar compost associations.

Biochar (BC) has been proven effective in promoting the production of safety food in cadmium (Cd)-polluted soil and the impact can be further enhanced through interaction with compost (CM). However, there existed unclear impacts of biochar with varying particle sizes in conjunction with compost on microbiome composition, rhizosphere functions, and soil health. Hence, in this study, two bulk-biochar derived from wood chips and pig manure were fabricated into nano-biochar using a ball-milling method. Subsequently, in a field experiment, the root-associated bacterial community and microbial functions of lettuce were evaluated in respond to Cd-contaminated soil remediated with nano/bulk-BCCM. The results showed that compared to bulk-BCCM, nano-BCCM significantly reduced the Cd concentration in the edible part of lettuce and the available Cd in the soil. Both nano-BCCM and bulk-BCCM strongly influenced the composition of bacterial communities in the four root-associated niches, and enhanced rhizosphere functions involved in nitrogen, phosphorus, and carbon cycling, as well as the relative abundance and biodiversity of keystone modules in rhizosphere soil. Furthermore, soil quality index analysis indicated that nano-BCCM exhibited greater potential than bulk-BCCM in maintaining soil health. The data revealed that nano-BCCM could regulate the Cd concentration in lettuce shoot by promoting microbial biodiversity of keystone modules in soil-root continuum and rhizosphere bacterial functions. These findings suggest that nano-biochar compost associations can be a superior strategy for enhancing microbial functions, maintaining soil health, and ensuring crop production safety in the Cd-contaminated soil compared to the mix of bulk-biochar and compost.

Intraspecific variation in tomato: Impact on production quality and cadmium phytoremediation efficiency in intercropping systems with hyperaccumulating plant.

Intercropping with hyperaccumulators can facilitate the safe utilization of cadmium-contaminated soil. However, the effectiveness of this approach is influenced by plant species and varieties, which necessitates research on optimal plant consortia. In this study, 8 tomato varieties (3 cherry tomatoes and 5 common large-fruit tomatoes) were intercropped with Sedum alfredii in a moderately Cd-contaminated vegetable field. The results showed that the Cd concentration in the fruits of common large-fruit tomato varieties under monoculture was 1.03-1.50 mg/kg, while that in the fruits of cherry tomato varieties was 0.67-0.71 mg/kg. After intercropping with S. alfredii, the fruit Cd concentrations of Hangza 501, Hangza 503, and Hangza 108 decreased by 16.42 %, 19.72 %, and 6.76 %, respectively, while those of the other varieties significantly increased, except for those of Hangza 8. In contrast, the shoot Cd concentration of cherry tomatoes was greater than that of large-fruit tomatoes under monoculture. Furthermore, a significant increase in the shoot Cd concentration was noted in the Hangza 501, Hangza 503 and Hangza 603 plants following intercropping. Additionally, intercropping with S. alfredii increased the concentration of soluble sugars in the fruits of Hangza 8, Hangza 501, Hangza 503 and Hangza 603 by 4.66 %, 17.91 %, 10.60 % and 17.88 %, respectively. Intercropping with tomatoes resulted in a decrease in both the biomass and Cd uptake of S. alfredii. Interestingly, the inhibitory effect on S. alfredii was less pronounced when intercropped with cherry tomatoes than when intercropped with large-fruit tomatoes. Among the intercropping treatments, S. alfredii exhibited the greatest total Cd accumulation (0.06 mg/plant) when intercropped with Hangza 503. In conclusion, the cherry tomato variety Hangza 503 was the most suitable for intercropping with S. alfredii and can be used safely for vegetable production and simultaneous phytoremediation of polluted soil. Our findings suggest that strategic selection of tomato varieties can optimize the effectiveness of "phytoextraction coupled with agro-safe production" technology for managing soil Cd concentrations.

Metagenomic insights into microbial metabolic mechanisms of a combined solid-phase denitrification and anammox process for nitrogen removal in mainstream wastewater treatment.

To overcome the significant challenges associated with nitrite supply and nitrate residues in mainstream anaerobic ammonium oxidation (anammox)-based processes, this study developed a combined solid-phase denitrification (SPD) and anammox process for low-strength nitrogen removal without the addition of nitrite. The SPD step was performed in a packed-bed reactor containing poly-3-hydroxybutyrate-co-3-hyroxyvelate (PHBV) prior to employing the anammox granular sludge reactor in the continuous-flow mode. The removal efficiency of total inorganic nitrogen reached 95.7 ± 1.2% under a nitrogen loading rate of 0.18 ± 0.01 kg N·m3·d-1, and it required 1.02 mol of nitrate to remove 1 mol of ammonium nitrogen. The PHBV particles not only served as biofilm carriers for the symbiosis of hydrolytic bacteria (HB) and denitrifying bacteria (DB), but also carbon sources that facilitated the coupling of partial denitrification and anammox in the granules. Metagenomic sequencing analysis indicated that Burkholderiales was the most abundant HB genus in SPD. The metabolic correlations between DB (Betaproteobacteria, Rhodocyclaceae, and Anaerolineae) and anammox bacteria (Candidatus Brocadiac and Kuenenia) in the granules were confirmed through microbial co-occurrence networks analysis and functional gene annotations. Additionally, the genes encoding nitrate reductase (Nap) and nitrite reductase (Nir) in DB primarily facilitated nitrate reduction, thereby supplying nitric oxide to anammox bacteria for subsequent nitrogen removal with hydrazine synthase (Hzs) and hydrazine dehydrogenase (Hdh). The findings provide insights into microbial metabolism within combined SPD and anammox processes, thus advancing the development of mainstream anammox-based processes in engineering applications.

Plant endophyte immobilization technology: A promising approach for chromium-contaminated water and soil remediation.

Microbial immobilization technology is considered an efficient bioremediation method for chromium (Cr) pollution. However, it is currently unclear which strain is more beneficial for the remediation of Cr-contaminated water and soil. Therefore, corn straw biochar was used as a carrier to prepare materials for fixing the endophytes Serratia sp. Y-13 (BSR1), Serratia nematodiphila (BSR2), Lysinibacillus sp. strain SePC-36 (BLB1), Lysinibacillus mangiferihumi strain WK63 (BLB2) and the commercial bacteria Shewanella oneidensis MR-1 (BSW). The results demonstrated that, compared with BSW, endophyte-loaded biochar (especially BSR1) was more effective at remediating Cr pollution in water and soil. Endophyte-loaded biochar reduced the abundance of soil pathogenic bacteria, enhanced the number of beneficial plant endophytes, reduced the soil Cr(VI) concentration, improved soil fertility, reduced the plant Cr concentration and improved the yield of lettuce. Redundancy analysis (RDA) and structural equation modelling (PLS-PM) suggested that soil microbes are closely related to soil Cr(VI), plant fresh weight and soil organic matter, whereas endophyte-loaded biochar directly influences plant cell motility pathways by altering plant microbes. This study represents a pioneering investigation into the efficacy of endophyte-loaded biochar as a remediation strategy for Cr pollution.

Dissipation-Induced Extended-Localized Transition.

A mobility edge (ME), representing the critical energy that distinguishes between extended and localized states, is a key concept in understanding the transition between extended (metallic) and localized (insulating) states in disordered and quasiperiodic systems. Here we explore the impact of dissipation on a quasiperiodic system featuring MEs by calculating steady-state density matrix and analyzing quench dynamics with sudden introduction of dissipation. We demonstrate that dissipation can lead the system into specific states predominantly characterized by either extended or localized states, irrespective of the initial state. Our results establish the use of dissipation as a new avenue for inducing transitions between extended and localized states and for manipulating dynamic behaviors of particles.

Evaluation of plasma-derived extracellular vesicles miRNAs and their connection with hippocampal mRNAs in alcohol use disorder.

Alcohol use disorder (AUD) is a common mental illness with high morbidity and disability. The discovery of laboratory biomarkers has progressed slowly, resulting in suboptimal diagnosis and treatment of AUD. This study aimed to identify promising biomarkers, as well as the potential miRNA-mRNA networks associated with AUD pathogenesis. RNA sequencing was performed on plasma-derived small extracellular vesicles (sEVs) from AUD patients and healthy controls (HCs) to harvest miRNAs expression profiles. Machine learning (ML) models were built to screen characteristic miRNAs, whose target mRNAs were analyzed using TargetScan, miRanda and miRDB databases. Gene Expression Omnibus (GEO) datasets (GSE181804 and GSE180722) providing postmortem hippocampal gene expression profiles of AUD subjects were mined. A total of 247 differentially expressed (DE) plasma-derived sEVs miRNAs and 122 DE hippocampal mRNAs were obtained. Then, 22 overlapping sEVs miRNAs with high importance scores were gained by intersecting 5 ML models. As a result, we established a putative sEVs miRNA-hippocampal mRNA network that can effectively distinguish AUD patients from HCs. In conclusion, we proposed 5 AUD-representative sEVs miRNAs (hsa-miR-144-5p, hsa-miR-182-5p, hsa-miR-142-5p, hsa-miR-7-5p, and hsa-miR-15b-5p) that may participate in the pathogenesis of AUD by modulating downstream target hippocampal genes. These findings may provide novel insights into the diagnosis and treatment of AUD.

CRISPR/Cas13a-based supersensitive circulating tumor DNA assay for detecting EGFR mutations in plasma.

Despite recent technological advancements in cell tumor DNA (ctDNA) mutation detection, challenges persist in identifying low-frequency mutations due to inadequate sensitivity and coverage of current procedures. Herein, we introduce a super-sensitivity and specificity technique for detecting ctDNA mutations, named HiCASE. The method utilizes PCR-based CRISPR, coupled with the restriction enzyme. In this work, HiCASE focuses on testing a series of EGFR mutations to provide enhanced detection technology for non-small cell lung cancer (NSCLC), enabling a detection sensitivity of 0.01% with 40 ng cell free DNA standard. When applied to a panel of 140 plasma samples from 120 NSCLC patients, HiCASE exhibits 88.1% clinical sensitivity and 100% specificity with 40 µL of plasma, higher than ddPCR and Super-ARMS assay. In addition, HiCASE can also clearly distinguish T790M/C797S mutations in different positions at a 1% variant allele frequency, offering valuable guidance for drug utilization. Indeed, the established HiCASE assay shows potential for clinical applications.

Identification of toll-like receptor 2 as a key regulator of neuronal apoptosis in vascular dementia by bioinformatics analysis and experimental validation.

BACKGROUND: Vascular dementia (VaD), the second most prevalent type of dementia, lacks a well-defined cause and effective treatment. Our objective was to utilize bioinformatics analysis to discover the fundamental disease-causing genes and pathological mechanisms in individuals diagnosed with VaD. METHODS: To identify potential pathogenic genes associated with VaD, we conducted weighted gene co-expression network analysis (WGCNA), differential expression analysis, and protein-protein interaction (PPI) analysis. The exploration of potential biological mechanisms involved the utilization of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. Moreover, a bilateral common carotid artery stenosis (BCAS) mouse model of VaD was established, and the expression of the hub gene, its relationship with cognitive function and its potential pathogenic mechanism were verified by cognitive behavior tests, cerebral blood flow measurement, Western blotting, and immunofluorescence experiments. RESULTS: This study identified 293 DEGs from the brain cortex of VaD patients and healthy controls, among these genes, the Toll-like receptor 2 (TLR2) gene was identified as hub gene, and it was associated with the apoptosis-related pathway PI3K/AKT.The BCAS model demonstrated that the use of TLR2 inhibitors greatly enhanced the cognitive function of the mice (p < 0.05). Additionally, there was a notable decrease in the number of apoptotic cells in the brain cortex of the mice (p < 0.01). Moreover, significant alterations in the levels of proteins related to the PI3K/AKT pathway and cleaved-caspase3 proteins were detected (p < 0.05). CONCLUSIONS: TLR2 plays a role in the pathophysiology of VaD by enhancing the neuronal apoptotic pathway, suggesting it could be a promising therapeutic target.

A LAMP-based hydrogen ion selective electrochemical sensor for highly sensitive detection of Mycoplasma pneumoniae.

A concise and rapid detection method for Mycoplasma pneumoniae is urgently required due to its severe impact on human health. To meet such a need, this study proposed and constructed an innovative point-of-care testing (POCT) platform that consists of a hydrogen ion-selective loop-mediated isothermal amplification (H+-LAMP) sensor and an electrochemical detection device. The H+-LAMP sensor successfully integrated the working and reference electrodes and converted the H+ generated during the LAMP process into an electrochemical signal. High sensitivity and stability for pathogen detection were also achieved by treating the working electrode with an electrodeposited polyaniline solid contact layer and by using an ion-selective membrane. As a result, the sensor shows a sensitivity of 68.26 mV per pH, a response time of less than 2 s, and a potential drift of less than 5 mV within one hour, which well meets the urgent need. The results also demonstrated that the detection limit for Mycoplasma pneumoniae was lowered to 1 copy per µL, the nucleic acid extraction and detection process could be completed in 30 minutes, and the impact of interfering ions on the sensor was negligible. Validation with 20 clinical samples yielded satisfactory results. More importantly, the storage lifespan of such an electrochemical sensor is over seven days, which is a great advantage for on-site pathogen detection. Therefore, the hydrogen ion-selective sensor constructed in this investigation is particularly suitable as a core component for instant pathogen detection platforms.

CSF1R blockade slows progression of cerebral hemorrhage by reducing microglial proliferation and increasing infiltration of CD8 + CD122+ T cells into the brain.

Microglia play a pivotal role in the neuroinflammatory response after brain injury, and their proliferation is dependent on colony-stimulating factors. In the present study, we investigated the effect of inhibiting microglia proliferation on neurological damage post intracerebral hemorrhage (ICH) in a mouse model, an aspect that has never been studied before. Using a colony-stimulating factor-1 receptor antagonist (GW2580), we observed that inhibition of microglia proliferation significantly ameliorated neurobehavioral deficits, attenuated cerebral edema, and reduced hematoma volume after ICH. This intervention was associated with a decrease in pro-inflammatory factors in microglia and an increased infiltration of peripheral regulatory CD8 + CD122+ T cells into the injured brain tissue. The CXCR3/CXCL10 axis is the mechanism of brain homing of regulatory CD8 + CD122+ T cells, and the high expression of IL-10 is the hallmark of their synergistic anti-inflammatory effect with microglia. And activated astrocytes around the insult site are a prominent source of CXCL10. Thus, inhibition of microglial proliferation offers a new perspective for clinical translation. The cross-talk between multiple cells involved in the regulation of the inflammatory response highlights the comprehensive nature of neuroimmunomodulation.

Construction of GPC3-modified Lipopolymer SiRNA Delivery System.

BACKGROUND: Gene therapy has been widely concerned because of its unique therapeutic mechanism. However, due to the lack of safe and effective carries, it has not been widely used in clinical practice. Glypican 3 (GPC3) is a highly specific proteoglycan for hepatocellular carcinoma and is a potential diagnostic and therapeutic target for hepatocellular carcinoma. Herein, to monitor the effect of gene therapy and enhance the transfection efficiency of gene carriers, GPC3-modified lipid polyethyleneimine-modified superparamagnetic nanoparticle (GLPS), a type of visualized carrier for siRNA (small-interfering RNA) targeting the liver, was prepared. METHODS: We performed in vitro gene silencing, cytotoxicity, and agarose gel electrophoresis to identify the optimal GLPS formulation. In vitro MRI and Prussian blue staining verified the liver-targeting function of GLPS. We also analyzed the biocompatibility of GLPS by co-culturing with rabbit red blood cells. Morphological changes were evaluated using HE staining. RESULTS: The GLPS optimal formulation consisted of LPS and siRNA at a mass ratio of 25:1 and LPS and DSPE-PEG-GPC3 at a molar ratio of 2:3. GLPS exhibited evident liver-targeting function. In vitro, we did not observe morphological changes in red blood cells or hemolysis after co-culture. In vivo, routine blood analysis revealed no abnormalities after GLPS injection. Moreover, the tissue morphology of the kidney, spleen, and liver was normal without injury or inflammation. CONCLUSION: GLPS could potentially serve as an effective carrier for liver-targeted MRI monitoring and siRNA delivery.

An SSVEP-based BCI with 112 targets using frequency spatial multiplexing.

Objective.Brain-computer interface (BCI) systems with large directly accessible instruction sets are one of the difficulties in BCI research. Research to achieve high target resolution (⩾100) has not yet entered a rapid development stage, which contradicts the application requirements. Steady-state visual evoked potential (SSVEP) based BCIs have an advantage in terms of the number of targets, but the competitive mechanism between the target stimulus and its neighboring stimuli is a key challenge that prevents the target resolution from being improved significantly.Approach.In this paper, we reverse the competitive mechanism and propose a frequency spatial multiplexing method to produce more targets with limited frequencies. In the proposed paradigm, we replicated each flicker stimulus as a 2 × 2 matrix and arrange the matrices of all frequencies in a tiled fashion to form the interaction interface. With different arrangements, we designed and tested three example paradigms with different layouts. Further we designed a graph neural network that distinguishes between targets of the same frequency by recognizing the different electroencephalography (EEG) response distribution patterns evoked by each target and its neighboring targets.Main results.Extensive experiment studies employing eleven subjects have been performed to verify the validity of the proposed method. The average classification accuracies in the offline validation experiments for the three paradigms are 89.16%, 91.38%, and 87.90%, with information transfer rates (ITR) of 51.66, 53.96, and 50.55 bits/min, respectively.Significance.This study utilized the positional relationship between stimuli and did not circumvent the competing response problem. Therefore, other state-of-the-art methods focusing on enhancing the efficiency of SSVEP detection can be used as a basis for the present method to achieve very promising improvements.

Global insights into endophytic bacterial communities of terrestrial plants: Exploring the potential applications of endophytic microbiota in sustainable agriculture.

Endophytic microorganisms are indispensable symbionts during plant growth and development and often serve functions such as growth promotion and stress resistance in plants. Therefore, an increasing number of researchers have applied endophytes for multifaceted phytoremediation (e.g., organic pollutants and heavy metals) in recent years. With the availability of next-generation sequencing technologies, an increasing number of studies have shifted the focus from culturable bacteria to total communities. However, information on the composition, structure, and function of bacterial endophytic communities is still not widely synthesized. To explore the general patterns of variation in bacterial communities between plant niches, we reanalyzed data from 1499 samples in 30 individual studies from different continents and provided comprehensive insights. A group of bacterial genera were commonly found in most plant roots and shoots. Our analysis revealed distinct variations in the diversity, composition, structure, and function of endophytic bacterial communities between plant roots and shoots. These variations underscore the sophisticated mechanisms by which plants engage with their endophytic microbiota, optimizing these interactions to bolster growth, health, and resilience against stress. Highlighting the strategic role of endophytic bacteria in promoting sustainable agricultural practices and environmental stewardship, our study not only offers global insights into the endophytic bacterial communities of terrestrial plants but also underscores the untapped potential of these communities as invaluable resources for future research.

Effect of destability time on microstructure and properties of hypoeutectic high chromium cast iron.

The present work investigated the effect of destabilization time on the mechanical properties and microstructure evolution of high chromium cast iron, and scanning electron microscopy and electron probe microanalysis techniques were employed. The results show that the hardness of hypoeutectic high chromium cast iron is related to the size and volume fraction of secondary carbides precipitated from the matrix. The hardness of the alloy continues to rise due to the continuous increase of the volume fraction of the secondary carbide at the initial stage of destabilization. The alloy reaches its peak hardness value at 950 °C and 1000 °C for 1 hour holding time. The solid solubility of carbon and alloying elements in the matrix increases as the holding time extends, resulting in a large number of carbides redissolved into the matrix, making the hardness of the alloy decrease; the hardness of the alloy at 14 h is less than that at 10 min. Under 1050 °C, the size and density of the secondary carbide increase significantly; extending the holding time will lead to the continuous reduction of the carbide rod that provides strength, thus, the hardness curve shows a downward trend.

[Liujunzi Decoction treats 4NQO-induced esophageal cancer in mice: a study based on serum metabolomics].

This study aims to explore the mechanism of Liujunzi Decoction in the treatment of 4-nitroquinoline-N-oxide(4NQO)-induced esophageal cancer in mice. One hundred mice of 35-45 days were randomized into blank, model, and low-, medium-, and high-concentration(18.2, 36.4, and 54.6 g·kg~(-1), respectively) Liujunzi Decoction groups. The mice in other groups except the blank group had free access to the water containing 100 µg·mL~(-1) 4NQO for 16 weeks for the modeling of esophageal cancer. The mice in the Liujunzi Decoction groups were fed with the diets supplemented with corresponding concentrations of Liujunzi Decoction. The body weight and organ weights were weighed for the calculation of organ indexes. The pathological changes of the esophageal tissue were observed by hematoxylin-eosin(HE) staining. Ultra performance liquid chromatography-mass spectrometry(UPLC-MS/MS) was employed to collect metabolites from mouse serum samples, screen out potential biomarkers, and predict related metabolic pathways. Compared with the blank group, the model group showed decreased spleen and stomach indexes and increased lung, esophagus, and kidney indexes. Compared with the model group, Liujunzi Decoction groups had no significant changes in the organ indexes. The HE staining results showed that Liujunzi Decoction inhibited the invasive growth and cancerization of the esophageal cancer cells. A total of 9 potential biomarkers of Liujunzi Decoction in treating esophageal cancer were screened out in this study, which were urocanic acid, 1-oleoylglycerophosphoserine, 11-deoxy prostaglandin E1, Leu-Glu-Lys-Glu,(±) 4-hydroxy-5E,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid, ureidosuccinic acid,(2R)-2,4-dihydroxy-3,3-dimethylbutanoic acid, kynurenic acid, and bicyclo prostaglandin E2, which were mainly involved in histidine, pyrimidine, alanine, aspartate, glutamate, pantothenate and tryptophan metabolism and coenzyme A biosynthesis. In summary, Liujunzi Decoction may exert the therapeutic effect on the 4NQO-induced esophageal cancer in mice by regu-lating the amino acid metabolism, inflammation, and immune function.

Non-Noble-Metal-Doped Carbon Nitride Photocatalysts for Water Splitting Screened Out by Empty Defect States and the d-Band Center.

A rational design of water-splitting photocatalysts from the perspective of the electronic structure is highly desirable for optimizing catalytic activities. However, the structure-activity relationship is still unclear, which impedes the development of efficient catalysts. Herein, by comparing systematically the overall water-splitting capability of 20 kinds of metallic elements anchored at three sites (including cavity, carbon vacancy, and nitrogen vacancy) of graphitic carbon nitride (g-C3N4) through density functional theory calculations, we uncover that availability of in-gap empty defect states and the d-band center position are paramount parameters to determine activities of g-C3N4 on photocatalytic water splitting. In-gap empty states play a role in accommodating electrons from H2O to facilitate its splitting. A lower d-band center weakens the interaction between reaction intermediates and g-C3N4, thereby promoting O2 desorption. Metals embedded at carbon vacancies are found to be superior to those at cavities and nitrogen vacancies because the former not only provides ample in-gap empty states but also has a lower d-band center. We also discover a rule that, for a reaction in which the bond order between the metal and intermediate enlarges (reduces), its reaction difficulty increases (decreases) with the increasing atomic number for elements in the same period. After screening, we find that non-noble metals Co, Ni, and Ga anchored at carbon vacancies possess catalytic performances comparable to Pd- and Pt-doped systems, with the rate-determining barriers less than 0.55 eV. Our findings may provide useful information for designing effective photocatalysts.

Tumor margin irregularity degree is an important preoperative predictor of adverse pathology for clinical T1/2 renal cell carcinoma and the construction of predictive model.

PURPOSE: To explore the critical role of the tumor margin irregularity degree (TMID) of renal tumors in predicting adverse pathology of patients with clinical T1/2 (cT1/2) renal cell carcinoma (RCC). METHODS: A total of 821 patients with cT1/2 RCC undergoing nephrectomy in the Second Hospital of Tianjin Medical University between January 2017 and December 2020 were reviewed. The tumor margin irregularity (TMI) was classified into renal mass with locally raised protrusion and smooth margin called 'lobular', sharply and unsmooth nodular margin called 'spiculation', blurred margins between tumor and renal parenchyma or a completely irregular and non-elliptical shape. The ratio between the number of irregular cross-sections (X) and the number of total cross-sections from top to bottom occupied (Y) was defined as TMID (X/Y). The logistic regression was performed to determine the independent predictors of adverse pathology, and the Kaplan-Meier curve and log-rank test were used to analyze the survival outcomes. RESULTS: Among 821 cT1/2 RCC patients, 245 (29.8%) had adverse pathology. The results of the univariate and multivariate logistic regressions showed that the age, tumor size, hemoglobin, and TMID were the independent predictors of adverse pathology. Incorporation of TMID could increase the discrimination of the predictive model with the area under curve (AUC) of ROC curves increasing from 0.725 to 0.808. Patients with adverse pathology or higher TMID both had significantly shorter recurrence-free survival (RFS). CONCLUSION: The nomogram model incorporated with TMID for predicting adverse pathology could increase its discrimination, calibration, and clinical application values, compared with the models without TMID.