Construction of a Zygosaccharomyces rouxii strain overexpressing the QOR gene for increased HDMF production.

4-Hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF) is a flavor compound widely found in natural products and is used in food as a flavor-enhancing agent. Quinone oxidoreductase (QOR) was verified as a key enzyme to synthesize HDMF in strawberry, while its impact on HDMF production by Zygosaccharomyces rouxii was still unknown. The QOR gene was cloned and overexpressed in Z. rouxii, and its impact on HDMF production by Z. rouxii was then further analyzed. At the same time, it is expected to obtain engineered strains of Z. rouxii with high HDMF production. The results showed that the engineered strains of Z. rouxii exhibit different levels of QOR gene expression and HDMF production; among them, the QOR6 strain exhibiting the highest gene expression level and HDMF production was named as ZrQOR. The HDMF production of the ZrQOR strain was significantly higher than that of wild-type Z. rouxii at 3 and 5 days of culture, with 1.41-fold and 1.08-fold increases, respectively. At 3 days of fermentation, the highest HDMF yield of ZrQOR strain was obtained (2.75 mg/L), 2 days ahead of the reported highest HDMF production by Z. rouxii. At 3, 5, and 7 days, QOR gene expression was 4.8-fold, 3.3-fold, and 5.6-fold higher in the ZrQOR strain than in the wild-type Z. rouxii, respectively. Therefore, overexpression of the QOR gene facilitates HDMF synthesis. The genetic stability of the 0-20 generation ZrQOR strain was stable, and there was no significant difference in colony shape, QOR expression, or HDMF production compared to the wild type. In this study, the genetic engineering Z. rouxii strain was used to improve HDMF production. This research has laid the groundwork for further industrial production of HDMF via microbial synthesis.

Lower micromolar activity of the antifungal imidazoles on the bacterial-type bifunctional aldehyde/alcohol dehydrogenase (AdhE) in Cryptosporidium parvum and in vitro efficacy against the zoonotic parasite.

Cryptosporidium parvum is a waterborne and foodborne zoonotic protozoan parasite, a causative agent of moderate to severe diarrheal diseases in humans and animals. However, fully effective treatments are unavailable for medical and veterinary uses. There is a need to explore new drug targets for potential development of new therapeutics. Because C. parvum relies on anaerobic metabolism to produce ATP, fermentative enzymes in this parasite are attractive targets for exploration. In this study, we investigated the ethanol-fermentation in the parasite and characterized the basic biochemical features of a bacterial-type bifunctional aldehyde/alcohol dehydrogenase, namely CpAdhE. We also screened 3892 chemical entries from three libraries and identified 14 compounds showing >50% inhibition on the enzyme activity of CpAdhE. Intriguingly, antifungal imidazoles and unsaturated fatty acids are the two major chemical groups among the top hits. We further characterized the inhibitory kinetics of selected imidazoles and unsaturated fatty acids on CpAdhE. These compounds displayed lower micromolar activities on CpAdhE (i.e., IC50 values ranging from 0.88 to 11.02 µM for imidazoles and 8.93 to 35.33 µM for unsaturated fatty acids). Finally, we evaluated the in vitro anti-cryptosporidial efficacies and cytotoxicity of three imidazoles (i.e., tioconazole, miconazole and isoconazole). The three antifungal imidazoles exhibited lower micromolar efficacies against the growth of C. parvum in vitro (EC50 values ranging from 4.85 to 10.41 µM and selectivity indices ranging from 5.19 to 10.95). The results provide a proof-of-concept data to support that imidazoles are worth being further investigated for potential development of anti-cryptosporidial therapeutics.

Identification and Characterization of Metastasis-Initiating Cells in ESCC in a Multi-Timepoint Pulmonary Metastasis Mouse Model.

Metastasis is the biggest obstacle to esophageal squamous cell carcinoma (ESCC) treatment. Single-cell RNA sequencing analyses are applied to investigate lung metastatic ESCC cells isolated from pulmonary metastasis mouse model at multiple timepoints to characterize early metastatic microenvironment. A small population of parental KYSE30 cell line (Cluster S) resembling metastasis-initiating cells (MICs) is identified because they survive and colonize at lung metastatic sites. Differential expression profile comparisons between Cluster S and other subpopulations identified a panel of 7 metastasis-initiating signature genes (MIS), including CD44 and TACSTD2, to represent MICs in ESCC. Functional studies demonstrated MICs (CD44high) exhibited significantly enhanced cell survival (resistances to oxidative stress and apoptosis), migration, invasion, stemness, and in vivo lung metastasis capabilities, while bioinformatics analyses revealed enhanced organ development, stress responses, and neuron development, potentially remodel early metastasis microenvironment. Meanwhile, early metastasizing cells demonstrate quasi-epithelial-mesenchymal phenotype to support both invasion and anchorage. Multiplex immunohistochemistry (mIHC) staining of 4 MISs (CD44, S100A14, RHOD, and TACSTD2) in ESCC clinical samples demonstrated differential MIS expression scores (dMISs) predict lymph node metastasis, overall survival, and risk of carcinothrombosis.

Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress.

OBJECTIVE: Hepatolenticular degeneration (HLD) is an autosomal recessive disorder that manifests as multiorgan damage due to impaired copper (Cu) metabolism. Female patients with HLD often experience reproductive impairments. This study investigated the protective effect of berberine against ovarian damage in toxic-milk (TX) mice, a murine model for HLD. METHODS: Mice were categorized into control group, HLD TX group (HLD group), penicillamine (Cu chelator)-treated TX group and berberine-treated TX group. Body weight, ovary weight and the number of ovulated eggs were recorded. Follicular morphology and cellular ultrastructure were examined. Total iron, ferrous iron (Fe2+) and trivalent iron (Fe3+) levels, as well as malondialdehyde (MDA), glutathione (GSH) and oxidized glutathione (GSSG), were measured in the ovaries. Western blot analysis was used to analyze the expression of proteins related to ferroptosis and endoplasmic reticulum (ER) stress. RESULTS: Ovarian tissue damage was evident in the HLD group, with a significant increase in ferroptosis and ER stress compared to the control group. This damage was inhibited by treatment with penicillamine, a Cu chelator. Compared with the HLD group, berberine increased the number of ovulations, and improved ovarian morphology and ultrastructure. Further, we found that berberine reduced total iron, Fe2+, MDA and GSSG levels, elevated GSH levels, decreased the expression of the ferroptosis marker protein prostaglandin-endoperoxide synthase 2 (PTGS2), and increased glutathione peroxidase 4 (GPX4) expression. Furthermore, berberine inhibited the expression of ER stress-associated proteins mediated by the protein kinase RNA-like ER kinase (PERK) pathway. CONCLUSION: Ferroptosis and ER stress are involved in Cu-induced ovarian damage in TX mice. Berberine ameliorates ovarian damage in HLD TX mice by inhibiting ferroptosis and ER stress. Please cite this article as: Liu QZ, Han H, Fang XR, Wang LY, Zhao D, Yin MZ, Zhang N, Jiang PY, Ji ZH, Wu LM. Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress. J Integr Med. 2024; Epub ahead of print.

Undescribed steroidal alkaloids from the bulbs of Fritillaria ussuriensis Maxim and their anti-inflammatory activities.

In total, 16 undescribed steroidal alkaloids (1-16), along with nine known ones (17-25), were isolated from the bulbs of Fritillaria ussuriensis Maxim. Among the undescribed compounds mentioned, compounds 1-6, 8 bearing an 16ß-hydroxy substituent, as well as compounds 13 and 14 exhibited an unusual seven-membered skeleton. Their structures were established based on extensive spectroscopic analyses, including HRESIMS and NMR (1D and 2D), and comparison with the data reported in the literature. Furthermore, all the compounds were evaluated for their anti-inflammatory effect on the NO production of LPS-stimulated RAW264.7 cells. Compounds 1, 4, 11, 15, 22 and 24 could significantly inhibit NO production with IC50 values below 10 µM.

Association of inflammatory trajectory with subarachnoid hemorrhage mortality.

OBJECTIVE: White blood cells (WBC) play an important role in the inflammatory response of the body. Elevated WBC counts on admission in patients with subarachnoid hemorrhage (SAH) correlate with a poor prognosis. However, the role of longitudinal WBC trajectories based on repeated WBC measurements during hospitalization remains unclear. We explored the association between different WBC trajectory patterns and in-hospital mortality. METHODS: We analyzed a cohort of consecutive patients with SAH between 2012 and 2020. Group-based trajectory modeling (GBTM) was used to group the patients according to their white blood cell patterns over the first 4 days. Stabilized inverse probability treatment weighting (sIPTW) was used to balance baseline demographic and clinical characteristics. We analyzed the association between the WBC trajectory groups and in-hospital mortality using a Cox proportional hazards model. RESULTS: In total, 506 patients with SAH were included in this retrospective cohort. The final model identified two distinct longitudinal WBC trajectories. After adjusting for confounding factors, multivariate regression analysis suggested that an elevated longitudinal WBC trajectory increased the risk of in-hospital mortality (hazard ratio [HR], 2.476; 95% confidence interval [CI] 1.081-5.227; P = 0.024) before sIPTW, and (HR, 2.472; 95%CI 1.489-4.977; P = 0.018) after sIPTW. CONCLUSION: In patients with SAH, different clinically relevant groups could be identified using WBC trajectory analysis. The WBC count trajectory-initially elevated and then decreased- may lead to an increased risk of in-hospital mortality following SAH.

CC4S: Encouraging Certainty and Consistency in Scribble-Supervised Semantic Segmentation.

Deep learning-based solutions have achieved impressive performance in semantic segmentation but often require large amounts of training data with fine-grained annotations. To alleviate such requisition, a variety of weakly supervised annotation strategies have been proposed, among which scribble supervision is emerging as a popular one due to its user-friendly annotation way. However, the sparsity and diversity of scribble annotations make it nontrivial to train a network to produce deterministic and consistent predictions directly. To address these issues, in this paper we propose holistic solutions involving the design of network structure, loss and training procedure, named CC4S to improve Certainty and Consistency for Scribble-Supervised Semantic Segmentation. Specifically, to reduce uncertainty, CC4S embeds a random walk module into the network structure to make neural representations uniformly distributed within similar semantic regions, which works together with a soft entropy loss function to force the network to produce deterministic predictions. To encourage consistency, CC4S adopts self-supervision training and imposes the consistency loss on the eigenspace of the probability transition matrix in the random walk module (we named neural eigenspace). Such self-supervision inherits the category-level discriminability from the neural eigenspace and meanwhile helps the network focus on producing consistent predictions for the salient parts and neglect semantically heterogeneous backgrounds. Finally, to further improve the performance, CC4S uses the network predictions as pseudo-labels and retrains the network with an extra color constraint regularizer on pseudo-labels to boost semantic consistency in color space. Rich experiments demonstrate the excellent performance of CC4S. In particular, under scribble supervision, CC4S achieves comparable performance to those from fully supervised methods. Comprehensive ablation experiments verify the effectiveness of the design choices in CC4S and its robustness under extreme supervision cases, i.e., when scribbles are shrunk proportionally or dropped randomly. The code for this work has been open-sourced at https://github.com/panzhiyi/CC4S.

Clinical domain knowledge-derived template improves post hoc AI explanations in pneumothorax classification.

OBJECTIVE: Pneumothorax is an acute thoracic disease caused by abnormal air collection between the lungs and chest wall. Recently, artificial intelligence (AI), especially deep learning (DL), has been increasingly employed for automating the diagnostic process of pneumothorax. To address the opaqueness often associated with DL models, explainable artificial intelligence (XAI) methods have been introduced to outline regions related to pneumothorax. However, these explanations sometimes diverge from actual lesion areas, highlighting the need for further improvement. METHOD: We propose a template-guided approach to incorporate the clinical knowledge of pneumothorax into model explanations generated by XAI methods, thereby enhancing the quality of the explanations. Utilizing one lesion delineation created by radiologists, our approach first generates a template that represents potential areas of pneumothorax occurrence. This template is then superimposed on model explanations to filter out extraneous explanations that fall outside the template's boundaries. To validate its efficacy, we carried out a comparative analysis of three XAI methods (Saliency Map, Grad-CAM, and Integrated Gradients) with and without our template guidance when explaining two DL models (VGG-19 and ResNet-50) in two real-world datasets (SIIM-ACR and ChestX-Det). RESULTS: The proposed approach consistently improved baseline XAI methods across twelve benchmark scenarios built on three XAI methods, two DL models, and two datasets. The average incremental percentages, calculated by the performance improvements over the baseline performance, were 97.8% in Intersection over Union (IoU) and 94.1% in Dice Similarity Coefficient (DSC) when comparing model explanations and ground-truth lesion areas. We further visualized baseline and template-guided model explanations on radiographs to showcase the performance of our approach. CONCLUSIONS: In the context of pneumothorax diagnoses, we proposed a template-guided approach for improving model explanations. Our approach not only aligns model explanations more closely with clinical insights but also exhibits extensibility to other thoracic diseases. We anticipate that our template guidance will forge a novel approach to elucidating AI models by integrating clinical domain expertise.

Decoupling the correlation between cytotoxic and exhausted T lymphocyte states enhances melanoma immunotherapy response prediction.

Cytotoxic T lymphocyte (CTL) and terminal exhausted T lymphocyte (ETL) activities crucially influence immune checkpoint inhibitor (ICI) response. Despite this, the efficacy of ETL and CTL transcriptomic signatures for response prediction remains limited. Investigating this across the TCGA and publicly available single-cell cohorts, we find a strong positive correlation between ETL and CTL expression signatures in most cancers. We hence posited that their limited predictability arises due to their mutually canceling effects on ICI response. Thus, we developed DETACH, a computational method to identify a gene set whose expression pinpoints to a subset of melanoma patients where the CTL and ETL correlation is low. DETACH enhances CTL's prediction accuracy, outperforming existing signatures. DETACH signature genes activity also demonstrates a positive correlation with lymphocyte infiltration and the prevalence of reactive T cells in the tumor microenvironment (TME), advancing our understanding of the CTL cell state within the TME.

Enhancing the selectivity for light olefins through catalytic cracking of n-hexane by phosphorus doping on lanthanum-modified ZSM-5.

Naphtha, as the primary raw material in the production of light olefins, could well accommodate their increasing demand through the energy-efficient process of catalytic cracking with ZSM-5. In the current work, different amounts of lanthanum and phosphorous were loaded on ZSM-5 using the wet impregnation method to tune the acidic properties of ZSM-5 for selective catalytic cracking of n-hexane to produce light olefins. Various characterization techniques such as X-ray diffraction (XRD), Al nuclear magnetic resonance (NMR), temperature-programmed desorption of NH3 (NH3-TPD), Py-Fourier transform infra-red (Py-FTIR), inductively coupled plasma optical emission spectroscopy (ICP-OES), N2 adsorption-desorption, X-ray photoelectron spectra (XPS), and scanning electron microscopy were adopted to investigate the modified zeolites. It was found that adding La to ZSM-5 (0.25 wt% to 1 wt%) improved the catalytic life and increased the n-hexane conversion (to 99.7%), while the further addition had a negative impact, reducing the conversion rate and deviating the product selectivity towards a substantial, undesired benzene, toluene, and xylene (BTX) fraction (33%). On the other hand, a 64% selectivity for light olefins was achieved on phosphorous-doped ZSM-5 (at a loading amount of 1 wt%) while reducing the BTX fraction (2.3%) and converting 69% of the n-hexane. A dual metal-modified ZSM-5 with optimal loading amount, 1P0.25LaZ5 (phosphorus 1 wt% and La 0.25 wt%), helped boost the light olefin selectivity to 62% in the tuned Lewis acid sites at an n-hexane conversion of about 77% while decreasing the undesired BTX selectivity to 3% by reducing the number of Brønsted sites. Thus, the current study reveals that tuning the acidic sites of ZMS-5 by dual metal augmentation with P.La is an effective way of controlling the amount of undesirable BTX produced at a stable n-hexane conversion rate and substantial olefin selectivity.

Study of Mechanical Properties of Sand Layer Grouting Reinforcement under Seawater Erosion.

Grouting serves as an effective method for mitigating geotechnical disasters in subsea tunnels. However, current theories and designs, primarily based on terrestrial tunnel contexts, seldom address the long-term effects of seawater ion erosion on reinforcement. An improved sand permeation grouting simulation test system was employed to examine the mechanical property evolution of sand layer grouting reinforcement under seawater erosion utilizing various grout types. The mechanical properties of grouting reinforcement, under varying curing conditions, were analyzed using a uniaxial compression test, permeability test, and scanning electron microscope (SEM) test. Test results indicate that seawater curing conditions initially enhance the strength and impermeability of grouting reinforcement; however, prolonged curing diminishes these mechanical benefits. The onset of this process occurs significantly sooner in cement-sodium silicate grout (28-56 days) compared to cement grout (56d to 90d). For the cement grouting reinforcement, the deformation modulus increases over time, albeit at a decreasing rate. The deformation modulus of cement-sodium silicate grouting reinforcement follows an increase-decrease-increase pattern, correlating with the volume ratio over time. The decline in mechanical properties of grouting reinforcement during the test's mid to late stages under seawater conditions results from the interplay between erosive ions, which inhibit mechanical growth and accelerate deterioration.

Non-Clinical Safety Evaluation of Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells in Cynomolgus Monkeys.

Purpose: In recent years, exosomes have been proved to be used to treat many diseases. However, due to the lack of uniform quality control standards for exosomes, the safety of exosomes is still a problem to be solved, especially now more and more exosomes are used in clinical trials, and its non-clinical safety evaluation is particularly important. However, there is no safety evaluation standard for exosomes at present. Therefore, this study will refer to the evaluation criteria of therapeutic biological products, adopt non-human primates to evaluate the non-clinical safety of human umbilical cord mesenchymal stem cell exosomes from the general pharmacology and immunotoxicity, aiming at establishing a safety evaluation system of exosomes and providing reference for the clinical application of exosomes in the future. Methods: 3.85 × 1012 exosomes derived from human umbilical cord mesenchymal stem cells were injected into cynomolgus monkeys intravenously. The changes of general clinical conditions, hematology, immunoglobulin, Th1/Th2 cytokines, T lymphocytes and B lymphocytes, and immune organs were observed before and within 14 days after injection. Results: The results showed that exosomes did not have obvious pathological effects on the general clinical conditions, blood, coagulation function, organ coefficient, immunoglobulin, Th1/Th2 cytokines, lymphocytes, major organs, and major immune organs (spleen, thymus, bone marrow) of cynomolgus monkeys. However, the number of granulocyte-macrophage colonies in exosomes group was significantly higher than that in control group. Conclusion: To sum up, the general pharmacological results and immunotoxicity results showed that the injection of 3.85 × 1012 exosomes may have no obvious adverse reactions to cynomolgus monkeys. This dose of exosomes is relatively safe for treatment, which provides basis research for non-clinical safety evaluation of exosomes and provides reliable research basis for future clinical application of exosomes.

Characterisation of aroma compounds, sensory characteristics, and bioactive components of a new type of huangjiu fermented with Chinese wild rice (Zizania latifolia).

Chinese wild rice (CWR) is a nutritious and healthy whole grain, worth developing. To develop and use its value, a new type of huangjiu was brewed with CWR, and the flavour characteristics, sensory quality, functional and bioactive components were evaluated. CWR (67 flavour substances) and glutinous rice (GR)-CWR huangjiu (62 flavour substances) had a better flavour than GR huangjiu (54 flavour substances), and the overall style of GR-CWR huangjiu was more skewed towards GR. The fruity, honey, caramel-like, herb and smoky aroma attributes of CWR huangjiu were higher than those of GR huangjiu (P < 0.05), while only the alcoholic was weaker (P < 0.05) due to the lower alcohol content. The huangjiu brewed using CWR had a better taste than that brewed using only GR. Furthermore, CWR huangjiu had the highest content of total dietary fiber (732.0 ± 15.2 mg/100 g), followed by GR-CWR (307.0 ± 8.5 mg/100 g), and GR (127.0 ± 2.3 mg/100 g). CWR huangjiu also had the highest total phenolic compounds (3.32 ± 0.05 mg/100 g/%vol) and total saponins (2.46 ± 0.03 mg/100 g/%vol) contents, followed by GR-CWR and GR. This study provides guidance for exploring further possibilities for CWR in the future.

Novel strategy to quantify the viability of oocysts of Cryptosporidium parvum and C. hominis, a risk factor of the waterborne protozoan pathogens of public health concern.

While waters might be contaminated by oocysts from >40 Cryptosporidium species, only viable oocysts of C. parvum and C. hominis truly pose the main health risk to the immunocompetent population. Oocyst viability is also an important but often neglected risk factor in monitoring waterborne parasites. However, commonly used methods in water monitoring and surveys cannot distinguish species (microscopic observation) or oocyst viability (PCR), as dead oocysts in water could retain gross structure and DNA content for weeks to months. Here, we report new TaqMan qRT-PCR/qPCR assays for quantitative detection of viable C. parvum and C. hominis oocysts. By targeting a hypothetical protein-encoding gene cgd6_3920 that is highly expressed in oocysts and variable between species, the qRT-PCR/qPCR assays achieve excellent analytical specificity and sensitivity (limit of quantification [LOQ] = 0.25 and 1.0 oocyst/reaction). Using calibration curves, the number and ratio of viable oocysts in specimens could be calculated. Additionally, we also establish a TaqMan-18S qPCR for cost-effective screening of pan-Cryptosporidium-positive specimens (LOQ = 0.1 oocyst/reaction). The assay feasibility is validated using field water (N = 43) and soil (79) specimens from 17 locations in Changchun, China, which detects four Cryptosporidium species from seven locations, including three gp60-subtypes (i.e., IIdA19G1, IIdA17G1 and IIdA24G2) of C. parvum oocysts showing varied viability ratios. These new TaqMan q(RT)-PCR assays supplement current methods in the survey of waters and other samples (e.g., surfaces, foods and beverages), and are applicable to assessing the efficiency of oocyst deactivation protocols.

Mandibular Osteomyelitis as the Earliest Clinical Manifestation of Maxillary Sinus Lymphoma.

Extranodal natural killer/T-cell lymphoma is a distinct subtype of non-Hodgkin lymphoma that originates from natural killer cells or cytotoxic T cells. Its diagnosis is challenging due to the rarity and lack of awareness, especially in cases where osteomyelitis of the jawbone is the initial symptom. This paper reports a case of extranodal natural killer/T-cell lymphoma presenting primarily with oral ulcers. Through analyzing the clinical and pathological characteristics, differential diagnosis, treatment and prognosis, and reasons for misdiagnosis of the disease, this study aims to provide references for clinical diagnosis and treatment.

Effects of low protein feed on hepato-intestinal health and muscle quality of grass carp (Ctenopharyngodon idellus).

In this study, grass carp (33.28 ± 0.05 g) were fed three diets for 8 weeks: control (crude protein [CP] 30%, crude lipid [CL] 6%), low protein (LP; CP16%, CL6%), and low protein with high-fat (LPHF; CP16%, CL10%). The final body weight decreased in the LP and LPHF groups compared to the Control (P < 0.05). Liver triglycerides, total cholesterol, and nonesterified fatty acids were higher in the LP group than the Control, whereas these indexes in the LPHF group were higher than those in the LP group (P < 0.05). The LP group had intestinal barrier damage, while the LPHF group had a slight recovery. TNF-α, IL-8, and IL-1ß content were lower in the LP group than in the Control (P < 0.05), and even higher in the LPHF group (P < 0.05). The expressions of endoplasmic reticulum stress-related genes Activating transcription factor 6 (ATF-6) and Glucose-regulated protein (GRP78) were higher in the LPHF group against the LP group (P < 0.05). The IL-1ß and TNF-α content negatively correlated with intestinal Actinomycetes and Mycobacterium abundance (P < 0.05). The muscle fiber diameter was smaller in both the LP and LPHF groups than the control (P < 0.05), with the LP group showing metabolites related to protein digestion and absorption, and LPHF group exhibiting metabolites related to taste transmission. The results demonstrate reducing dietary protein affects growth, causing liver lipid accumulation, reduced enteritis response, and increased muscle tightness, while increasing fat content accelerates fat accumulation and inflammation.

Electrostatic doping tunable magnetic transition and half-metallicity in the monolayer CrCTe3.

The electrical manipulation of the magnetic transition and spin-polarized states has attracted extensive attention in the field of spintronics. In this work, we perform a detailed study on the electronic and magnetic properties of the carrier-doped monolayer CrCTe3by using first-principles calculation. It is found that, the magnetic transition from Néel-antiferomagnetic (nAFM) to ferromagnetic (FM) is observed in the case of the electron doping, while for hole doping a magnetic transition sequence of nAFM→zigzag-AFM→FM is observed in the monolayer CrCTe3. Interestingly, the carrier doping induced FM ground state always exhibits half-metallicity with full spin polarization. Moreover, the spin polarity of the half-metallic electronic states is opposite for electron and hole doping, meaning that the spin polarization direction can be tuned by manipulating a gate voltage. The Monte Carlo calculations show that the magnetic transition temperature of the doped FM CrCTe3is rapidly increased with the increasing doping concentration and is extremely expected to achieve room temperature at a suitable doping concentration. These findings demonstrate that the monolayer AFM system possesses a potential application in spintronic devices with electrically tunable spin polarization.

Moringin alleviates DSS-induced ulcerative colitis in mice by regulating Nrf2/NF-κB pathway and PI3K/AKT/mTOR pathway.

Ulcerative colitis (UC) is a main form of inflammatory bowel disease (IBD), which is a chronic and immune-mediated inflammatory disease. Moringin (MOR) is an isothiocyanate isolated from Moringa oleifera Lam., and has been recognized as a promising potent drug for inflammatory diseases and antibacterial infections. The present study investigated the role of moringin in dextran sulfate sodium (DSS)-induced UC mice. Mouse colitis was induced by adding DSS to the drinking water for seven consecutive days. Our experimental results showed that MOR relieves DSS-induced UC in mice by increasing body weight and colonic length, and reducing the disease activity index and histological injury. Mechanistically, MOR improves intestinal barrier function by increasing the expression of tight junction proteins (TJPs) and enhancing the secretion of mucin in DSS-induced mice. MOR inhibits inflammatory response and intestinal damage by regulating Nrf2/NF-κB signaling pathway and modulating the PI3K/AKT/mTOR pathway. Furthermore, in Nrf2 knockout (Nrf2-/-) mice, the protective effects of MOR on DSS-induced UC were abolished. Meanwhile, treatment with MOR reduced inflammation and cell damage via regulating Nrf2/NF-κB pathway in a lipopolysaccharide (LPS)-induced inflammation model of Caco-2 cells. In contrast, ML385, an Nrf2 inhibitor, might eliminate the protection provided by MOR. Notably, treatment with MOR significantly up-regulated the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), suggesting that MOR may be a potential PPAR-γ activator. In conclusion, MOR exerts protective effect in UC by improving intestinal barrier function, regulating Nrf2/NF-κB and PI3K/AKT/mTOR signaling pathways, and another effect associated with the regulation of PPAR-γ expression.

Identification of candidate genes for Fusarium head blight resistance from QTLs using RIL population in wheat.

Fusarium head blight (FHB) stands out as one of the most devastating wheat diseases and leads to significantly grain yield losses and quality reductions in epidemic years. Exploring quantitative trait loci (QTL) for FHB resistance is a critical step for developing new FHB-resistant varieties. We previously constructed a genetic map of unigenes (UG-Map) according to the physical positions using a set of recombinant-inbred lines (RILs) derived from the cross of 'TN18 × LM6' (TL-RILs). Here, the number of diseased spikelets (NDS) and relative disease index (RDI) for FHB resistance were investigated under four environments using TL-RILs, which were distributed across 13 chromosomes. A number of 36 candidate genes for NDS and RDI from of 19 stable QTLs were identified. The average number of candidate genes per QTL was 1.89, with 14 (73.7%), two (10.5%), and three (15.8%) QTLs including one, two, and 3-10 candidate genes, respectively. Among the 24 candidate genes annotated in the reference genome RefSeq v1.1, the homologous genes of seven candidate genes, including TraesCS4B02G227300 for QNds/Rdi-4BL-4553, TraesCS5B02G303200, TraesCS5B02G303300, TraesCS5B02G303700, TraesCS5B02G303800 and TraesCS5B02G304000 for QNds/Rdi-5BL-9509, and TraesCS7A02G568400 for QNds/Rdi-7AL-14499, were previously reported to be related to FHB resistance in wheat, barely or Brachypodium distachyon. These genes should be closely associated with FHB resistance in wheat. In addition, the homologous genes of five genes, including TraesCS1A02G037600LC for QNds-1AS-2225, TraesCS1D02G017800 and TraesCS1D02G017900 for QNds-1DS-527, TraesCS1D02G018000 for QRdi-1DS-575, and TraesCS4B02G227400 for QNds/Rdi-4BL-4553, were involved in plant defense responses against pathogens. These genes should be likely associated with FHB resistance in wheat.

Metabolism-inflammasome crosstalk shapes innate and adaptive immunity.

Inflammasomes are a central component of innate immunity and play a vital role in regulating innate immune response. Activation of inflammasomes is also indispensable for adaptive immunity, modulating the development and response of adaptive immunity. Recently, increasing studies have shown that metabolic alterations and adaptations strongly influence and regulate the differentiation and function of the immune system. In this review, we will take a holistic view of how inflammasomes bridge innate and adaptive (especially T cell) immunity and how inflammasomes crosstalk with metabolic signals during the immune responses. And, special attention will be paid to the metabolic control of inflammasome-mediated interactions between innate and adaptive immunity in disease. Understanding the metabolic regulatory functions of inflammasomes would provide new insights into future research directions in this area and may help to identify potential targets for inflammasome-associated diseases and broaden therapeutic avenues.