Identification and validation of tumor-specific T cell receptors from tumor infiltrating lymphocytes using tumor organoid co-cultures.

T cell receptor-engineered T cells (TCR-Ts) therapy is promising for cancer immunotherapy. Most studies have focused on identifying tumor-specific T cell receptors (TCRs) through predicted tumor neoantigens. However, current algorithms for predicting tumor neoantigens are unreliable and many neoantigens are derived from non-coding regions. Thus, the technological platform for identifying tumor-specific TCRs using natural antigens expressed on tumor cells is urgently needed. In this study, tumor organoids-enriched tumor infiltrating lymphocytes (oeT) were obtained by repeatedly stimulation of autologous patient-derived organoids (PDO) in vitro. The oeT cells specifically responded to autologous tumor PDO by detecting CD137 expression and the secretion of IFN-γ using enzyme-linked immunospot assay. The measurement of oeT cell-mediated killing of three-dimensional organoids was conducted using a caspase3/7 flow cytometry assay kit. Subsequently, tumor-specific T cells were isolated based on CD137 expression and their TCRs were identified through single-cell RT-PCR analysis. The specificity cytotoxicity of TCRs were confirmed by transferring to primary peripheral blood T cells. The co-culture system proved highly effective in generating CD8+ tumor-specific oeT cells. These oeT cells effectively induced IFN-γ secretion and exhibited specificity in killing autologous tumor organoids, while not eliciting a cytotoxic response against normal organoids. The analysis conducted by TCRs revealed a significant expansion of T cells within a specific subset of TCRs. Subsequently, the TCRs were cloned and transferred to peripheral blood T cells generation engineered TCR-Ts, which adequately recognized and killed tumor cell in a patient-specific manner. The co-culture system provided an approach to generate tumor-specific TCRs from tumor-infiltrating lymphocytes of patients with colorectal cancer, and tumor-specific TCRs can potentially be used for personalized TCR-T therapy.

Machine learning-based prediction model of acute kidney injury in patients with acute respiratory distress syndrome.

BACKGROUND: Acute kidney injury (AKI) can make cases of acute respiratory distress syndrome (ARDS) more complex, and the combination of the two can significantly worsen the prognosis. Our objective is to utilize machine learning (ML) techniques to construct models that can promptly identify the risk of AKI in ARDS patients. METHOD: We obtained data regarding ARDS patients from the Medical Information Mart for Intensive Care III (MIMIC-III) and MIMIC-IV databases. Within the MIMIC-III dataset, we developed 11 ML prediction models. By evaluating various metrics, we visualized the importance of its features using Shapley additive explanations (SHAP). We then created a more concise model using fewer variables, and optimized it using hyperparameter optimization (HPO). The model was validated using the MIMIC-IV dataset. RESULT: A total of 928 ARDS patients without AKI were included in the analysis from the MIMIC-III dataset, and among them, 179 (19.3%) developed AKI after admission to the intensive care unit (ICU). In the MIMIC-IV dataset, there were 653 ARDS patients included in the analysis, and among them, 237 (36.3%) developed AKI. A total of 43 features were used to build the model. Among all models, eXtreme gradient boosting (XGBoost) performed the best. We used the top 10 features to build a compact model with an area under the curve (AUC) of 0.850, which improved to an AUC of 0.865 after the HPO. In extra validation set, XGBoost_HPO achieved an AUC of 0.854. The accuracy, sensitivity, specificity, positive prediction value (PPV), negative prediction value (NPV), and F1 score of the XGBoost_HPO model on the test set are 0.865, 0.813, 0.877, 0.578, 0.957 and 0.675, respectively. On extra validation set, they are 0.724, 0.789, 0.688, 0.590, 0.851, and 0.675, respectively. CONCLUSION: ML algorithms, especially XGBoost, are reliable for predicting AKI in ARDS patients. The compact model maintains excellent predictive ability, and the web-based calculator improves clinical convenience. This provides valuable guidance in identifying AKI in ARDS, leading to improved patient outcomes.

A Two-Phase Feature Selection Method for Identifying Influential Spreaders of Disease Epidemics in Complex Networks.

Network epidemiology plays a fundamental role in understanding the relationship between network structure and epidemic dynamics, among which identifying influential spreaders is especially important. Most previous studies aim to propose a centrality measure based on network topology to reflect the influence of spreaders, which manifest limited universality. Machine learning enhances the identification of influential spreaders by combining multiple centralities. However, several centrality measures utilized in machine learning methods, such as closeness centrality, exhibit high computational complexity when confronted with large network sizes. Here, we propose a two-phase feature selection method for identifying influential spreaders with a reduced feature dimension. Depending on the definition of influential spreaders, we obtain the optimal feature combination for different synthetic networks. Our results demonstrate that when the datasets are mildly or moderately imbalanced, for Barabasi-Albert (BA) scale-free networks, the centralities' combination with the two-hop neighborhood is fundamental, and for Erdos-Rényi (ER) random graphs, the centralities' combination with the degree centrality is essential. Meanwhile, for Watts-Strogatz (WS) small world networks, feature selection is unnecessary. We also conduct experiments on real-world networks, and the features selected display a high similarity with synthetic networks. Our method provides a new path for identifying superspreaders for the control of epidemics.

Effect of high soil C/N ratio and nitrogen limitation caused by the long-term combined organic-inorganic fertilization on the soil microbial community structure and its dominated SOC decomposition.

The application of organic fertilizers, such as straw and manure, is an efficient approach to maintain soil productivity. However, the effect of these organic fertilizers on soil microbial nutrient balance has not yet been established. In this study, the effects of the long-term combined organic-inorganic fertilization on microbial community were investigated by conducting a 30-year-long field test. Overall, the following five fertilizer groups were employed: inorganic NP fertilizer (NP), inorganic NK fertilizer (NK), inorganic NPK fertilizer (NPK), NPK + manure (MNPK), and NPK + straw (SNPK). The results indicated that the mean natural logarithm of the soil C:N:P acquisition enzyme ratio was 1.04:1.11:1.00 under organic-inorganic treatments, which showed a deviation from its overall mean ratio of 1:1:1. This indicates that microbial resources do not have a balance. Vector analysis (vector angle <45°) and threshold elemental ratio analysis (RC:N-TERC:N > 0) further demonstrated that the microbial metabolism was limited by Nitrogen (N) under SNPK and MNPK treatments. N limitation further influenced soil microbial community structure and its dominated SOC decomposition. Specifically, Microbial communities transformed into a more oligotrophic-dominant condition (fungal, Acidobacteria, Chloroflexi) from copiotrophic-dominant (Proteobacteria, Actinobacteria) condition with increasing N limitation. Lysobacter genus and Blastocatellaceae family, in the bacterial communities along with the Mortierella elongata species in fungal communities, were markedly associated with the N limitation, which could be the critical biomarker that represented N limitation. Both correlation analysis and partial least squares path modeling showed significant positive effects of N limitation on the ratio of bacterial functional genes (Cellulase/Amylase), involved in recalcitrant SOC degradation.

Lateral monolayer MoS2 homojunction devices prepared by nitrogen plasma doping.

Monolayer MoS2 possesses good electron mobility, structural flexibility and a direct band gap, enabling it to be a promising candidate for flexible and wearable optoelectronic devices. In this article, the lateral monolayer MoS2 homojunctions were prepared by a nitrogen plasma selective doping technique. The monolayer MoS2 thin films were synthesized by chemical vapor deposition and characterized by photoluminescence, atom force microscope and Raman spectroscopy. The electronic and photoelectric properties of the lateral pn and npn homojunctions were discussed. The results showed that the rectifying ratio of the pn homojunction diode is ∼103. As a photodetector of pn homojunction, the optical responsivity is up to 48.5 A W-1, the external quantum efficiency is 11 301%, the detectivity is ∼109 Jones and the response time is 20 ms with the laser of 532 nm and the reverse bias voltage of 10 V. As a bipolar junction transistor of npn homojunction, the amplification coefficient reached ∼102. A controllable plasma doping technique, compatible with traditional CMOS process, is utilized to realize the monolayer MoS2 based pn and npn homojunctions, and it propels the potential applications of 2D materials in the electronic, optoelectronic devices and circuits.

Adipose-derived stem cells and cancer cells fuse to generate cancer stem cell-like cells with increased tumorigenicity.

Adipose-derived stem cells (ADSCs) are a type of mesenchymal stem cells isolated from adipose tissue and have the ability to differentiate into adipogenic, osteogenic, and chondrogenic lineages. Despite their great therapeutic potentials, previous studies showed that ADSCs could enhance the proliferation and metastatic potential of breast cancer cells (BCCs). In this study, we found that ADSCs fused with BCCs spontaneously, while breast cancer stem cell (CSC) markers CD44+ CD24-/low EpCAM+ were enriched in this fusion population. We further assessed the fusion hybrid by multicolor DNA FISH and mouse xenograft assays. Only single nucleus was observed in the fusion hybrid, confirming that it was a synkaryon. In vivo mouse xenograft assay indicated that the tumorigenic potential of the fusion hybrid was significantly higher than that of the parent tumorigenic triple-negative BCC line MDA-MB-231. We had compared the fusion efficiency between two BCC lines, the CD44-rich MDA-MB-231 and the CD44-poor MCF-7, with ADSCs. Interestingly, we found that the fusion efficiency was much higher between MDA-MB-231 and ADSCs, suggesting that a potential mechanism of cell fusion may lie in the dissimilarity between these two cell lines. The cell fusion efficiency was hampered by knocking down the CD44. Altogether, our findings suggest that CD44-mediated cell fusion could be a potential mechanism for generating CSCs.

Acute exposure to triphenyl phosphate inhibits the proliferation and cardiac differentiation of mouse embryonic stem cells and zebrafish embryos.

Attention has recently paid to the interaction of triphenyl phosphate (TPHP) and body tissues, particularly within the reproductive and development systems, due to its endocrine-disrupting properties. However, the acute effects of TPHP on early embryonic development remain unclear. Here, we used mouse embryonic stem cells (mESC) and zebrafish embryos to investigate whether TPHP is an embryo toxicant. First, we found that continuous exposure of TPHP decreased the proliferation and increased the apoptotic populations of mESCs in a concentration-dependent manner. Results of mass spectrometry showed that the intracellular concentration of TPHP reached 39.45 ± 7.72 µg/g w/w after 3 hr of acute exposure with TPHP (38.35 µM) but gradually decreased from 3 hr to 48 hr. Additionally, DNA damage was detected in mESCs after a short-term treatment with TPHP, which in turn, activated DNA damage responses, leading to cell cycle arrest by changing the expression levels of p53, proliferating cell nuclear antigen, and Y15-phosphorylated Cdk I. Furthermore, our results revealed that short-term treatment with TPHP disturbed cardiac differentiation by decreasing the expression levels of Oct4, Sox2, and Nanog and transiently reduced the glycolysis capacity in mESCs. In zebrafish embryos, exposure to TPHP resulted in broad, concentration-dependent developmental defects and coupled with heart malformation and reduced heart rate. In conclusion, the two models demonstrate that acute exposure to TPHP affects early embryonic development and disturbs the cardiomyogenic differentiation.

Oxidative Rearrangement Mechanism of Pentalenolactone F Catalyzed by Cytochrome P450 CYP161C2 (PntM).

The CYP161C2 (PntM) from Streptomyces arenae is a member of the cytochrome P450 enzymes, which catalyzes the unusual oxidative rearrangement of pentalenolactone F (1) to the sesquiterpenoid antibiotic pentalenolactone (3). On the basis of the crystal structure of PntM bound with substrate, quantum mechanical/molecular mechanics (QM/MM) calculations have been performed to explore the detailed mechanism of PntM-catalyzed oxidative rearrangement. The conversion from pentalenolactone F (1) to pentalenolactone (3) involves the stereospecific removal of the H-1 si from 1, the syn-1,2-migration of the 2 si methyl group, and the antarafacial loss of H-3 re. The abstraction of H-1 si by Cpd I is calculated to be rate limiting with an energy barrier of 20.3 kcal/mol, which basically agrees with the estimated free energy barrier from experiments (18.6 kcal/mol). It is the unfavorable geometry of Fe-OH-C1 that blocks the oxygen rebound reaction, and the subsequent intramolecular syn-1,2-methyl migration is accompanied by an electron transfer from the substrate to the porphyrin ring via an Fe-OH group, generating the carbocation intermediate. Owing to the positive charge, the intermediate can easily lose a proton to form the final products. Our calculation results indicate that both the carboxyl group of porphyrin and Fe-OH can act as bases to accept the proton of the substrate. The target product pentalenolactone and the three isomeric byproducts correspond to four different modes of deprotonation.

Protonation state and fine structure of the active site determine the reactivity of dehydratase: hydration and isomerization of ß-myrcene catalyzed by linalool dehydratase/isomerase from Castellaniella defragrans.

Linalool dehydratase/isomerase (LinD) from Castellaniella defragrans is a bifunctional enzyme that catalyzes the hydration of ß-myrcene to (S)-linalool and the isomerization of (S)-linalool to geraniol. In this paper, on the basis of recently obtained crystal structures, the catalytic mechanism of LinD has been explored by a combined quantum mechanics and molecular mechanics (QM/MM) approach. Two computational models have been constructed. Model I (LinD-linalool) was derived from the crystal structure of the selenomethionine derivative of LinD (Semet-LinD) in complex with the natural substrate geraniol, whereas model II (LinD-ß-myrcene) was constructed from the crystal structure of LinD in complex with ß-myrcene. In addition to a minor conformational difference of the active sites, the two models also differ in the protonation state of key residues. In model I, the pocket residue Asp39' was set to be deprotonated and His129 was protonated on ND1, whereas in model II, Asp38' was set to be deprotonated and His128 was protonated on NE2. Our calculations reveal model II as the active one, which implies that hydration and dehydration are sensitive to the protonation state and fine structure of the active site. On the basis of model II, the conversion details from ß-myrcene to geraniol can be obtained. Firstly, ß-myrcene is hydrated by a crystal water (W14) and is converted into the stable intermediate (S)-linalool, then linalool is isomerized to geraniol with an overall energy barrier of 24.6 kcal mol-1. Besides, linalool can also reversibly convert into the reactant with an energy barrier of 24.1 kcal mol-1. It is also found that the intermediate IM1 can directly transform to geraniol without first converting to (S)-linalool. His128 and Tyr65 form hydrogen bonds to stabilize the structure of the active site, but they do not act as general acid/base catalysts during the catalytic reactions.

Effects of home-based lower limb resistance training on muscle strength and functional status in stable Chronic obstructive pulmonary disease patients.

AIMS AND OBJECTIVES: This study aimed to determine the effect of home-based lower limb resistance training (LLRT) in patients with stable COPD. BACKGROUND: Pulmonary rehabilitation (PR) in COPD patients has been substantially investigated, but the rehabilitation components differ among studies. Few works have focused on home-based LLRT. Furthermore, few studies have assessed muscle strength and functional status by isokinetic/isometric extensor muscle peak torque (PT) and five-repetition sit-to-stand test (FTSST), respectively. DESIGN: A randomised controlled design was adopted. METHODS: (i) The home-based LLRT consisted of six sets of lower limb training cycles by self-gravity resistance and Thera-band resistance at 8-12RM, 20-30 min/session and 3 sessions/week for 12 weeks. (ii) The intervention group (n = 25) received routine PR guidance and home-based LLRT, whereas the control group (n = 22) received routine PR guidance only. The muscle strengths, FTSST durations, 6-min walking distances (6MWDs) and COPD assessment test results at enrolment and week 12 were compared. RESULTS: Relative to the baseline findings, all the indexes of muscle strength (isometric extensor muscle PT, isometric extensor muscle PT to body weight ratio [PT/BW], isokinetic extensor muscle PT and isokinetic extensor muscle PT/BW) did not significantly change in the intervention group. Meanwhile, no significant intragroup difference was noted among the indexes of muscle strength (except for isometric extensor muscle PT) in the control group. The FTSST decrease was significant between and within groups. By contrast, the 6MWD significantly increased within both groups, but not between the groups. The COPD assessment tool score decreased significantly within the intervention group. CONCLUSIONS: Compared with routine PR guidance, home-based LLRT can improve not only the muscle strength and exercise endurance but also the lower limb functional status. RELEVANCE TO CLINICAL PRACTICE: Our developed home-based LLRT intervention is simple, safe and feasible in stable COPD patients and could hence be promoted in clinical practice.

Insights into the unprecedented epoxidation mechanism of fumitremorgin B endoperoxidase (FtmOx1) from Aspergillus fumigatus by QM/MM calculations.

Fumitremorgin B endoperoxidase (FtmOx1) from Aspergillus fumigatus is the first reported α-ketoglutarate-dependent mononuclear non-haem iron enzyme that catalyzes the endoperoxide formation reaction, converting Fumitremorgin B to verruculogen. Experiments reveal that the molecular oxygen (O2) is incorporated into verruculogen without O-O bond scission, which differs from the currently known non-haem iron enzymes, but the mechanistic details are still unclear. In this paper, on the basis of the crystal structures of FtmOx1 in complex with either the co-substrate (α-ketoglutarate) or the substrate (fumitremorgin B), a ternary complex model of the enzyme-α-ketoglutarate-substrate has been constructed, and combined quantum mechanics and molecular mechanics (QM/MM) calculations have been performed to unravel the novel mechanism of FtmOx1. Our calculations indicate the quintet of the FeIV[double bond, length as m-dash]O complex as the ground state. The FeIV[double bond, length as m-dash]O complex firstly abstracts a hydrogen from the hydroxyl of Tyr228 to initiate the reaction, which corresponds to a lower energy barrier (9.1 kcal mol-1). If the FeIV[double bond, length as m-dash]O complex directly abstracts a hydrogen from C21 of the substrate, the energy barrier would increase to 33.9 kcal mol-1. When Tyr228 was mutated to Ala228, this energy barrier decreases to 24.0 kcal mol-1. In the subsequent reaction, the generated Tyr228 radical abstracts the hydrogen (H2) from C21 of the substrate with an energy barrier of 23.8 kcal mol-1. The second molecular oxygen binds to the C21 radical of the substrate in the active pocket and further completes the epoxidation with an energy barrier of 4.8 kcal mol-1. These results may provide useful information for understanding the reaction mechanism of FtmOx1 and provide guidance for further experimental investigations.

Experience and nursing needs of school-age children undergoing lumbar puncture during the treatment of acute lymphoblastic leukaemia: a descriptive and qualitative study.

AIMS AND OBJECTIVES: To describe experiences and nursing needs of school-age Chinese children undergoing lumbar puncture for the treatment of acute lymphoblastic leukaemia. BACKGROUND: Lumbar puncture is an invasive procedure, causing psychological changes and physical discomfort in patients. In a previous study, it was proved that distraction intervention, such as music therapy, relieves pain and anxiety. There is limited evidence regarding the experience and needs of school-age children during lumbar puncture after being diagnosed with acute lymphoblastic leukaemia. To minimise their anxiety and pain during the procedure, it is important to collect information directly from these children. DESIGN: A descriptive qualitative research. METHODS: Twenty-one school-age children with acute lymphoblastic leukaemia participated in semi-structured interviews at a Children's Hospital in China. Data were collected by an experienced and trained interviewer. Qualitative content analysis was chosen to describe experiences of children undergoing lumbar puncture. RESULTS: While undergoing lumbar puncture for the treatment of acute lymphoblastic leukaemia, school-age Chinese children experienced complex psychological feelings (fear, tension, helplessness, sadness and anxiety). They also experienced physical discomfort. They had multipolar needs, such as information, communication, respect, self-actualisation, environment and equipment. CONCLUSIONS: This study identified important areas that must be closely monitored by healthcare staff, performing lumbar puncture on acute lymphoblastic leukaemia children. Thus, a successful and smooth procedure can be performed on these patients, and their quality of life can be improved. RELEVANCE TO CLINICAL PRACTICE: The experiences described in this study contribute to a better understanding of the needs of acute lymphoblastic leukaemia children undergoing lumbar puncture. They also provide valuable information to professional medical care staff that develops future nursing assessments.

Inverse relationship between species competitiveness and intraspecific trait variability may enable species coexistence in experimental seedling communities.

Theory suggests that intraspecific trait variability may promote species coexistence when competitively inferior species have higher intraspecific trait variability than their superior competitors. Here, we provide empirical evidence for this phenomenon in tree seedlings. We evaluated intraspecific variability and plastic response of ten traits in 6750 seedlings of ten species in a three-year greenhouse experiment. While we observed no relationship between intraspecific trait variability and species competitiveness in competition-free homogeneous environments, an inverse relationship emerged under interspecific competition and in spatially heterogeneous environments. We showed that this relationship is driven by the plastic response of the competitively inferior species: Compared to their competitively superior counterparts, they exhibited a greater increase in trait variability, particularly in fine-root traits, in response to competition, environmental heterogeneity and their combination. Our findings contribute to understanding how interspecific competition and intraspecific trait variability together structure plant communities.

Preoperative Prediction of Metastatic Lymph Nodes Posterior to the Right Recurrent Laryngeal Nerve in cN0 Papillary Thyroid Carcinoma.

Background: The advantages of the dissecting the metastatic lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) remain a great deal of controversies in papillary thyroid carcinoma (PTC) patients without clinical evidence. The purpose of our retrospective research was to investigate the predictive factors of the LN-prRLN in cN0 PTC patients. Methods and Materials: Altogether 251 consecutive cN0 PTC participants accepted unilateral or bilateral thyroidectomy accompanied with LN-prRLN dissection between June 2020 and May 2023 were included in the research. Then, univariate and multivariate logical regression analysis were conducted to analyze the relationship between the LN-prRLN and these predictive factors, and a predictive model was also developed. Surgical complications of LN-prRLN dissection were also presented. Results: The rate of LN-prRLN was 17.9% (45/251) in cN0 PTC patients after the analysis of postoperative histology. The age <55 years, multifocality, microcalcification, and BRAFV600E mutation were identified to be predictive factors of LN-prRLN in cN0 PTC patients. The risk score for LN-prRLN was calculated: risk score = 1.192 × (if age <55 years) + 0.808 × (if multifocality) + 1.196 × (if microcalcification in nodule) + 0.918 × (if BRAFV600E mutation in nodule). The rates of the transient hypoparathyroidism and hoarseness were 1.2% (3/251) and 2.0% (5/251), respectively. Conclusion: The age <55 years, multifocality, microcalcification, and BRAFV600E mutation are independent predictors of the LN-prRLN in cN0 PTC patients. An effective predictive model was established for predicting the LN-prRLN in cN0 PTC patients, with the aim to better guide the surgical treatment of PTC. A thorough inspection of the lateral compartment is recommended in PTC patients with risk factors. The multicenter research with long-term follow-up should be carried out to ascertain the optimal surgical approach for patients with PTC.

Benefits and trade-offs of replacing inorganic fertilizer by organic substrate in crop production: A global meta-analysis.

Replacing inorganic fertilizer with organic substrate contributes to sustainable agricultural production capacity. However, the effects of organic substitution regimes (OSR) on global crop productivity, soil carbon (C) and nitrogen (N) losses and biofertility as function of environmental variables have not been systematically quantified. Here, we have conducted a meta-analysis of these effects using field data (211 papers with 852 observations) collected around the world. Results indicated that OSR increased crop productivity (3.04 %) and soil biofertility (soil qMBC, qMBN, microbial richness, Shannon and functionality by 11.4 %, 21.1 %, 10.2 %, 3.95 %, and 38.5 %, respectively), and reduced soil N losses (N2O emissions, NH3 volatilization and soil N leaching by 26.5 %, 26.1 %, and 33.8 %, respectively), but increased CO2 emissions (19.4 %), and paddy fields CH4 emissions (41.2 %). N rate was an important factor influencing crop productivity and soil biofertility response to OSR, and crop productivity and soil biofertility had a greater positive response at moderate substitution rates in acid soil and long-term trials, but full substitution significantly decreased crop yield. Furthermore, the increase in soil biofertility and crop yield saturated in ~10-14 and ~ 22 years after organic substrate input. The emissions of CO2, CH4, and N2O significantly increased with increasing substitution rates, while the opposite was true for N leaching. The NH3 volatilization response to OSR presented a positive effect in acidic and coarse texture soil. OSR was more beneficial in mitigating soil C and N loss response (except CO2 emissions) in uplands compared to paddy fields. Therefore, implementation of OSR requires site-specific strategies to better achieve a balance between increasing crop production and reducing environmental benefits. Given that the OSR improvement varies depending on environmental variables, we propose a predictive model to initially assess the potential for OSR improvement. This study will provide scientific guidance on the reasonable application of organic substrate in agroecosystems.

Remobilization of Cd caused by iron oxide phase transformation and Mn2+ competition after stabilization by nano zero valent iron.

Stabilization techniques are vital in controlling Cd soil pollution. Nano zero valent iron (nZVI) has been extensively utilized for Cd remediation owing to its robust adsorption and reactivity. However, the environmental stress-induced stability of Cd after nZVI addition remains unclear. A pot experiment was conducted to evaluate the Cd bioavailability in continuously flooded (130 d) soil after stabilization with nZVI. The findings indicated that nZVI application did not result in a decline in Cd concentration in rice, as compared to the no-nZVI control. Additionally, nZVI simultaneously increased the available Cd concentration, iron-manganese oxide-bound (OX) Mn fraction, and relative abundance of Fe(III)-reducing bacteria, but it decreased OX-Cd and Mn availability in soil. Cadmium in rice tissues was positively correlated with the available Cd in soil. The results of subsequent adsorption tests demonstrated that CdO was the product of Cd adsorption by the nZVI aging products. Conversely, Mn2+ decreased the adsorption capacity of Cd-containing solutions. These results underscore the crucial role of both biotic and abiotic factors in undermining the stabilization of nZVI under continuous flooding conditions. This study offers novel insights into the regulation of nZVI-mediated Cd stabilization efficiency in conjunction with biological inhibitors and functional modification techniques.

Synergistic Effects of Soil-Based Irrigation and Manure Substitution for Partial Chemical Fertilizer on Potato Productivity and Profitability in Semiarid Northern China.

Soil-based irrigation and the partial substitution of chemical fertilizers with manure are promising practices to improve water and nitrogen (N) use efficiency. We hypothesize that their combination would simultaneously benefit potato production, tuber quality and profitability. A two-year experiment was conducted in semiarid northern China to investigate the combined effects of three water treatments [rainfed (W0), soil-based irrigation (W1), conventional irrigation (W2)] and three N treatments [no N (N0), chemical N (N1), 25% manure substitution (N2)] on these indicators, and to perform a comprehensive evaluation and correlation analysis. The results showed that water and N treatments separately affected all indicators except vitamin C content. Compared to W2, W1 significantly increased water productivity by 12% and irrigation water use efficiency (IWUE) by 30% due to 10% lower evapotranspiration and 21% lower water use. However, W1 and W2 negatively affected crude protein content. Conversely, this was compensated by the combination with N1 and N2. There were slight differences between N1 and N2 for all indicators on average across water treatments, while under W1, N2 significantly increased leaf area index (LAI) and N recovery efficiency (REN) by 18% and 29.4%, respectively, over N1. Also, comprehensive evaluations showed that W1N2 performed best, with the highest tuber yield, profit and acceptable quality. This can be explained by the increase in LAI, IWUE and REN due to the positive correlations with tuber yield and net return. Consequently, soil-based irrigation combined with 25% manure substitution had complementary effects on tuber quality and synergistic effects on potato productivity and profitability.

SERS detection platform based on a nucleic acid aptamer-functionalized Au nano-dodecahedron array for efficient simultaneous testing of colorectal cancer-associated microRNAs.

A surface-enhanced Raman scattering (SERS) detection platform was constructed based on Au nano-dodecahedrons (AuNDs) functionalized with nucleic acid aptamer-specific binding and self-assembly techniques. SERS labels were prepared by modifying Raman signaling molecules and complementary aptamer chains and were bound on the aptamer-functionalized AuNDs array. Using this protocol, the limits of detection (LODs) of miR-21 and miR-18a in the serum were 6.8 pM and 7.6 pM, respectively, and the detection time was 5 min. Additionally, miR-21 and miR-18a were detected in the serum of a mouse model of colorectal cancer. The results of this protocol were consistent with quantitative real-time polymerase chain reaction (qRT-PCR). This method provides an efficient and rapid method for the simultaneous testing of miRNAs, which has great potential clinical value for the early detection of colorectal cancer (CRC).

Schistosoma japonicum scFv-IL18 fusion DNA ameliorates hepatic fibrosis in schistosomiasis-infected mice via improving local concentration of IL-18 in liver.

The pathogenesis of chronic schistosomiasis is caused by irritation of the schistosome eggs trapped in liver that induce delayed hypersensitive reactions from the surrounding tissues, leading to the formation of inflammatory granuloma and subsequent fibrosis. A Schistosoma japonicum (S. japonicum) single-chain fragment variable (SjscFv) which specifically binds to the S. japonicum soluble immature egg antigen (SIEA) can be used as a target to deliver specific cytokine towards the site of hepatic fibrosis. To test this hypothesis, a novel recombinant plasmid, pVAX1/SjscFv-IL18, was constructed by fusing SjscFv to IL-18 gene with a 45bp glycine-rich linker. Furthermore, experiments on mice showed that pVAX1/SjscFv-IL18 could effectively express IL-18 in the liver and in serum. Hepatic contents of IL-2 and IFN-γ (Th1-type) in S. japonicum-infected mice vaccinated with pVAX1/SjscFv-IL18 increased significantly but those of their IL-4 and IL-10 (Th2-type) decreased as compared to the analyzed results of 4 cytokines in the liver cells of control mice vccinated with pVAX1/IL18. Consistent with the levels of Th1 and Th2 cytokines, mice vaccinated with pVAX1/SjscFv-IL18 developed much less hepatic fibrosis 20weeks after infection, which was evaluated by average volumn of granuloma and collagen contents. These data suggested that the linkage of IL-18 to the target-specific SjscFv molecule appears to be a potentially promising trial route of therapy, the hepatic fibrosis in S. japonicum-infected mice may be ameliorated through effective expression of IL18 in liver.

A comparative study on the development of Chinese and English abilities of Chinese primary school students through two bilingual reading modes: human-AI robot interaction and paper books.

To address the challenges encountered by Chinese primary school students, particularly left-behind and migrant children, who exhibit a preference for animations, video games, and short videos over reading books and struggle with Chinese-English bilingual skills, this study introduces an educational robot AI-assisted method for simultaneous bilingual reading. To assess the effectiveness of this method, a 6-month Chinese-English bilingual extracurricular reading comparative experiment was conducted involving 85 grade 5 students from two classes in a primary school in Hangzhou, China. The AI-assisted class freely read 100 bilingual/English electronic picture books and 200 Chinese electronic classic serial picture books by employing the AI-assisted human-computer interactive electronic reading mode of the "Educational Robot+Audio Electronic Picture Book+Character-play Based Reading." In contrast, the paper book group read the same content presented in the traditional paper book format, following the "regular independent reading" mode. Post-experimental analyses were conducted employing t-tests and MANCOVA and the results revealed that: the primary factors influencing reading effectiveness are the choice of reading materials, reading tools, and reading mode, while reading time does not emerge as the principal influencing factor. Furthermore, students in the AI class demonstrated significant enhancements in bilingual reading motivation, reading amount, reading comprehension, independent learning ability, pronunciation proficiency, and test scores compared to their peers in the paper book class. The AI-assisted reading mode utilizing educational robots garnered positive feedback from teachers, parents, and students. It offers the potential to effectively substitute parental involvement in parent-child reading and English tutoring, while also enabling the simultaneous acquisition of bilingual proficiency in both Chinese and English. This approach proves to be highly effective, cost-efficient, and convenient, particularly for enhancing children's foreign language abilities. Moreover, it fosters positive reading habits and independent learning skills among primary school students, contributes to the establishment of lofty aspirations, and enhances bilingual performance. Overall, this innovative mode offers an effective means of facilitating children's acquisition of bilingualism and foreign language skills, as well as promoting reading education.